interleukin-8 and Multiple-Organ-Failure

Continuous hemofiltration currently represents standard renal replacement therapy in critically ill patients. Because higher ultrafiltration rates are related to better survival rates in experimental and clinical studies and hemofiltration results in fewer cardiovascular side effects than does conventional hemodialysis, the use of inflammatory mediator removal by this extracorporeal procedure has emerged. This article reviews clinically relevant principles of compound transport and the experimental and clinical effects of hemofiltration during sepsis. Hemofiltration did not have a major impact on plasma concentrations of prominent inflammatory cytokines (tumor necrosis factor-a and interleukins 1b, 6, and 8) and seems therefore not to be able to counterbalance endogenous cytokine production despite considerable cytokine removal in the filtrate. Contradictory results in the literature are discussed under the viewpoint of membrane-related sieving coefficients and plasma cytokine measurement. A significant reduction in plasma anaphylatoxin concentrations by hemofiltration is associated with impressive immunomodulatory and cardiodepressive ultrafiltrate effects. Thus far, however, the use of hemofiltration for nonrenal indications remains experimental and is not supported by controlled clinical trials. Modern strategies of blood purification that may be associated with a high degree of effectiveness for mediator removal (high-volume hemofiltration and heparin-induced extracorporeal lipoprotein-fibrinogen precipitation) are discussed.

Topics: Anaphylatoxins; Animals; Blood Component Removal; Endotoxemia; Hemofiltration; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Multiple Organ Failure; Sepsis; Tumor Necrosis Factor-alpha

Topics: Adult; Cytokines; Fatal Outcome; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Multiple Organ Failure; Rocky Mountain Spotted Fever; Tumor Necrosis Factor-alpha

The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring postburn inflammation is of paramount importance but, so far, there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As interleukin 8 (IL-8) is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict postburn sepsis, infections, and mortality. Plasma cytokines, acute-phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days after injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure [MOF], and mortality) were recorded. A cutoff level for IL-8 was determined using receiver operating characteristic analysis. Statistical significance is set at P < 0.05. Receiver operating characteristic analysis identified a cutoff level of 234 pg/mL for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cutoff and stratified into high (H) (n = 133) and low (L) (n = 335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area burned and incidence of MOF (P < 0.001). In the H group, IL-8 levels were able to predict sepsis (P < 0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute-phase responses compared with the L group (P < 0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients.

Topics: Adolescent; Biomarkers; Burns; Child; Child, Preschool; Female; Humans; Infections; Inflammation Mediators; Interleukin-8; Kaplan-Meier Estimate; Male; Multiple Organ Failure; Predictive Value of Tests; Prospective Studies; Sepsis

The aim of this study is to evaluate the impact of neutral microporous resin hemoperfusion on hemodynamic improvement, removal of inflammatory cytokines, and mortality in critical care patients with severe sepsis. Forty-four patients with severe sepsis or septic shock were randomized to HA type hemoperfusion treatment (N=24) or standard therapy (N=20). Those undergoing hemoperfusion treatment received HA330 hemoperfusion. We measured the plasma concentrations of IL-6 and IL-8 at the start of every hemoperfusion treatment, and the following parameters were compared between the control group and the hemoperfusion group on days 3, 7, and 14: hemodynamics (cardiac index, systemic vascular resistance index, heart rate, and mean arterial pressure); change of hematology and coagulation function; organ function; and the sequential organ failure assessment (SOFA) score. Hospital, 28-day, and ICU mortality were also observed. Patients treated with HA hemoperfusion showed a significant removal of plasma IL-6 and IL-8 over time while in the study. Patients in the HA group also demonstrated significant increases in cardiac index, systemic vascular resistant index, fast withdrawal of vasoactive agents and decreases in heart rate compared with the controls at days 3 and 7. Although there was no significant difference between the groups in organ dysfunction as assessed by SOFA scores from day 0 (baseline) to day 7, significant improvement can be demonstrated in the hemoperfusion group at day 14. There was no significant difference between the groups in 28-day mortality, hospital mortality, or length of hospital stay, but ICU mortality and the length of ICU stay in the HA group were markedly reduced. Hemoperfusion treatment using the HA type cartridge in sepsis is safe and it may improve organ dysfunction, ICU mortality, and shorten the length of ICU stay. Clinical significant removal of inflammatory cytokines such as IL-6 and IL-8 from circulation by hemoperfusion may contribute to improving a patient's outcome in an ICU.

Topics: Aged; Aged, 80 and over; Blood Pressure; Female; Heart Rate; Hemoperfusion; Hospital Mortality; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Sepsis; Severity of Illness Index; Shock, Septic; Survival; Time Factors

To evaluate the effect and timing of continuous blood purification (CBP) in treatment of acute renal failure (ARF) following cardiac-vascular surgery.. Twenty-five patients with ARF following cardiac-vascular surgery were divided into systematic inflammatory response syndrome (SIRS) Group (n = 13) and multiple organ dysfunction syndrome (MODS) Group (n = 12) according to the illness state prior to CBP and were divided into Group A (n = 5, with the APACHEIII score prior to CBP 90). All of the 25 patients underwent continuous veno-venous hemofiltration (CVVH). Before and 24h after the CVVH APACHEIII score was calculated and [peripheral; blood samples were collected to detect the levels of blood urea nitrogen (BUN) and serum creatinine (Scr) and the plasma levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha).. The APACHEIII score, BUN, Scr, IL6, IL8, and TNFalpha 24 h after the CBP of the 25 patients were 61 +/- 15 mmol/L, (19 +/- 5) mmol/L, (312 +/- 87) micromol/L, (544 +/- 154) ng/L, (18 +/- 7) ng/L, and (43 +/- 15) ng/L respectively, all significantly lower than those before CBP (81 +/- 20, 26 +/- 5 mmol/L, 458 +/- 107 micromol/L, (842 +/- 132) ng/L, (25 +/- 8) ng/L, and (59 +/- 17) ng/L respectively, all P = 0.000). The survival rate of SIRS Group was 84.62%, significantly higher than that of MODS Group (41.67%, P < 0.05). The APACHEIII score, and the levels of BUN, Scr, IL6, IL8, and TNF-alpha of Group MODS were significantly higher than those of Group SIRS. The higher the level of Scr, IL6, IL8, and TNF-alpha and the APACHEIII score the lower the survival rate.. CBP has a positive effect on ARF following cardiac-vascular surgery. The APACHEIII score 60 to 90 reflects an opportunity to treat the ARF following cardiac-vascular surgery using CBP.

Topics: Acute Kidney Injury; APACHE; Blood Urea Nitrogen; Cardiac Surgical Procedures; Humans; Interleukin-6; Interleukin-8; Multiple Organ Failure; Postoperative Complications; Renal Dialysis; Survival Analysis; Systemic Inflammatory Response Syndrome; Treatment Outcome; Tumor Necrosis Factor-alpha

To compare the hemodynamic and biological effects of high-adsorption continuous veno-venous hemofiltration (CVVH) with standard CVVH in septic shock.. In a randomized cross-over clinical trial twelve patients with septic shock and multiple organ failure were enrolled at a tertiary intensive care unit. Patients were allocated to either 9 hours of high-adsorption hemofiltration (CVVH with 3 hourly filter change using AN69 hemofilters - 3FCVVH) or 9 hours of standard hemofiltration (CVVH without filter change - 1F-CVVH).. Changes in hemodynamic variables, dose of noradrenaline required to maintain a mean arterial pressure greater than 75 mmHg and plasma concentrations of cytokines (IL-6, IL-8, IL-10 and IL-18) were measured. A 9-hour period of 3F-CVVH was associated with greater reduction in noradrenaline dose than a similar period of 1F-CVVH (median reduction: 16 vs. 3.5 microg/min, p=0.036; median percentage reduction: 48.1% vs. 17.5%, p=0.028). Unlike 1F-CVVH, 3F-CVVH was associated with a reduction in the plasma concentration of IL-6, IL-10 and IL-18 at 9 hours and a significant decrease 30 minutes after additional filter changes (IL-6: p<0.01, p<0.01; IL-10: p=0.03, p=0.016 and IL-18: p=0.016, p<0.01, respectively). Both, 3F-CVVH and 1F-CVVH were associated with decreased plasma concentrations of IL-8 at 9 hours (p<0.01, p<0.01, respectively). In a confirmatory ex-vivo experiment IL-6 concentrations substantially decreased during 3F-CVVH (at baseline 511 pg/mL and at end: 21 pg/mL) whereas IL-6 concentrations increased in control blood (at baseline 511 pg/mL and at end: 932 pg/mL).. High-adsorption CVVH appears more effective than standard CVVH in decreasing noradrenaline requirements and plasma concentrations of cytokines in septic shock patients.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Blood Pressure; Female; Heart Rate; Hemofiltration; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Norepinephrine; Renal Dialysis; Shock, Septic

Post-traumatic MOF results from local tissue injury because of migration and activation of dysfunctional polymorphonuclear leukocytes (PMN). Although fracture surgery exacerbates the postinjury inflammatory response, it is usually beneficial. This study compared changes in PMN receptor expression and migratory activity, in whole blood and following PMN isolation.. IL-8 mediated PMN migration and expression of CXCR-1, CD11b, and CD18 was studied in isolated and whole blood PMN in normal controls. Migration was studied at admission and day 5 after surgery in trauma patients undergoing fracture surgery.. PMN isolation results in increased expression of surface receptors and enhanced migration in normal controls. In trauma patient samples, isolated PMN migration is enhanced after injury, but suppressed when migration from whole blood is studied, both after injury and fracture surgery.. PMN isolation results in priming for migration, which has a relatively greater impact upon PMN in trauma patients. The observation that PMN activity may decline but priming potential remains enhanced is novel. Further refinements of whole blood and isolated PMN techniques are clearly warranted. This may help to resolve the mismatch in clinical and scientific experience in those patients with major fractures requiring surgical stabilization.

Topics: Adult; Femoral Fractures; Humans; Interleukin-8; Middle Aged; Multiple Organ Failure; Neutrophils; Receptors, Interleukin-8A; Tibial Fractures

Stress doses of hydrocortisone are known to have immunomodulatory effects in patients with hyperdynamic septic shock. The prognosis correlates with the presence and severity of septic encephalopathy. However, neurological evaluation is influenced by the use of analgesia sedation during artificial ventilation. The objective of this study was to demonstrate the effect of stress doses of hydrocortisone during the initial phase of human septic shock on the serum values of the neurospecific protein S-100B in comparison to the inflammation markers interleukin (IL)-8 in serum and polymorphonuclear (PMN) elastase in plasma. A total of 24 consecutive patients, who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock, were enrolled in this prospective, randomized, double-blind, single-center trial. The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. Multi-organ dysfunction syndrome was described by the Sepsis-related Organ Failure Assessment (SOFA) score. All patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/mL at study entry to 0.07 ng/mL 6 days later without significant differences compared to the placebo group. Initial IL-8 serum levels were significantly higher in the hydrocortisone group up to 12 h after study entry, and significantly decreased from 715 to 17 pg/mL at the end of the observation period. Median PMN elastase plasma levels were not affected by hydrocortisone infusion. Patients with initial S-100B serum levels > 0.50 ng/mL revealed significantly higher SOFA scores up to 30 h, IL-8 serum levels up to 12 h, and PMN elastase plasma levels up to 36 h after study entry than those patients with < or = 0.50 ng/mL. These effects were independent of the amount of fluid correction for hemodilution. Starting S-100B, IL-8 and PMN elastase values of the hydrocortisone group were within the ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. Stress doses of hydrocortisone resulted in a significant reduction in IL-8 serum, but not in S-100B serum and PMN elastase plasma concentration

Topics: Adult; Aged; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Germany; Humans; Hydrocortisone; Intensive Care Units; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Multiple Organ Failure; Nerve Growth Factors; Placebos; Prognosis; Prospective Studies; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Sensitivity and Specificity; Severity of Illness Index; Shock, Septic; Time Factors

Transfusion of stored packed red blood cells (PRBCs) has unintended effects beyond the desired results of increased oxygen delivery. A particular concern is the potential for lipid and cytokine mediators present in PRBCs to augment the postinjury inflammatory response that sometimes culminates in multiple organ failure. Through the use of a polymerized human hemoglobin (PolyHeme), we have been able to measure the inflammatory response in patients resuscitated with minimal exposure to banked components in the early postinjury period.. Critically injured patients requiring urgent transfusion were resuscitated with either PRBCs or PolyHeme in the early postinjury period. Proinflammatory cytokines (interleukin [IL]-8 and IL-6), counterregulatory cytokines (IL-10 and IL-11), and markers of endothelial injury (soluble intercellular adhesion molecule and soluble E-selectin) were serially measured.. Increases in IL-8, IL-6, and IL-10 were greater in patients resuscitated with PRBCs. IL-11 plasma levels were largely below the level of detection of the assay. There was no difference in markers of endothelial injury.. Consistent with concerns about the immunoinflammatory response to transfusion of PRBCs, we observed exaggerated levels of three markers associated with adverse outcome. The clinical significance of these findings with respect to the development of multiple organ failure awaits further study.

Topics: Adult; Biomarkers; Cell Adhesion Molecules; E-Selectin; Endothelium, Vascular; Erythrocyte Transfusion; Hemoglobins; Humans; Injury Severity Score; Interleukin-10; Interleukin-11; Interleukin-6; Interleukin-8; Multiple Organ Failure; Multiple Trauma; Prospective Studies; Resuscitation; Risk Factors; Treatment Outcome

To explore the effects of recombinant human growth hormone (rhGH) on the serum levels of cytokines in severely burned patients.. Thirty-six burn patients were enrolled in the study and were randomly divided into 3 groups according to the rhGH dosage used, i.e. small (0.3 IU.kg(-1).d(-1), A), large (0.6 IU.kg(-1).d(-1), B) dose groups and control group (C, with normal saline). The rhGH was administered beginning from 3 postburn days (PBDs) and lasted for 20 days. The dynamic changes in the serum levels of TNFalpha, IL-6, IL-8 and LPS at different time points were observed.. When compared with those in C group, the serum levels of TNFalpha, IL-6 in A, B groups were decreased, especially in B group with earlier decrease and bigger range (P < 0.01). Simultaneously, the serum LPS level was decreased accordingly with evident positive correlation with the change in those cytokines (r = 0.9723, P < 0.01). But there was no obvious difference in serum IL-8 level among A, B and C groups (P > 0.05).. rhGH might decrease the production of postburn inflammatory mediators, especially in higher dose in dose-dependent manner for some degree. The clinical application of rhGH might be a supplementary measure in preventing and ameliorating postburn SIRS and MODS in severely burned patients.

Topics: Adult; Burns; Cytokines; Dose-Response Relationship, Drug; Female; Human Growth Hormone; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Multiple Organ Failure; Recombinant Proteins; Survival Rate; Time Factors; Tumor Necrosis Factor-alpha

Conventional outcomes research provides only percentage risk of such end points as mortality rate, utilization of resources, and/or broad groupings of multiple organ system dysfunction. These prognostications generally are not applicable to individual patients. The purpose of the present study was to determine whether the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic variables, standard hospital laboratory tests, and circulating cytokine concentrations that predicted continuous and dichotomous dependent clinical variables, in advance, in individual patients with severe sepsis and septic shock, and whether these independent variables could be integrated into prospectively validated predictive models.. Data review and multivariate stepwise logistic regression.. University research laboratory.. Three hundred three patients with severe sepsis or septic shock who comprised the placebo arm of a multiple-institution clinical trial, who were randomly separated into a model building training cohort (n = 200) and a predictive cohort (n = 103).. None.. From baseline data and baseline plus serial input, including patient demographics, hospital laboratory tests, and plasma concentrations of interleukin-6, interleukin-8, and granulocyte colony stimulating factor, multiple regression models were developed that predicted clinically important continuous dependent variables quantitatively, in individual patients. Multivariate stepwise logistic regression was used to develop models that prognosticated dichotomous dependent end points. Data from individual patients in the predictive cohort were inserted into each predictive model for each day, with prospective validation accomplished by simple linear regression of individual predicted vs. observed values for continuous dependent variables, and by establishing the receiver operator characteristics area under the curve for logistic regression models that predicted dichotomous end points. Of SMART models for continuous dependent variables, 100 of 143 (70%) were validated at r values >.7 through day 3, and 184 of 259 (71%) above r =.5 through day 5. SMART predictions of dichotomous end points achieved receiver operator characteristics areas under the curve >.7 for up to 84% of the equations in the first week. Many SMART models for both continuous and dichotomous dependent variables were validated at clinically useful levels of accuracy as far as 28 days after baseline.. SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with severe sepsis and septic shock.

Topics: Clinical Laboratory Techniques; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-6; Interleukin-8; Logistic Models; Models, Theoretical; Multiple Organ Failure; Prognosis; Sepsis; Shock, Septic

Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis.. We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate.. Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups.. The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis

Topics: Acute Disease; Adult; Aged; Biomarkers; Double-Blind Method; E-Selectin; Female; Humans; Imidazoles; Interleukin-8; Length of Stay; Leucine; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Placebos; Platelet Activating Factor; Prospective Studies

Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects on septic multiple organ dysfunction in clinical and experimental studies. It was the aim of this study to determine whether continuous long-term AT III supplementation alters the systemic inflammatory response in patients with severe sepsis. In a prospective study, 29 surgical patients with severe sepsis were randomly assigned to receive either conventional intensive care treatment (n = 15, control group) or additional AT III supplementation to achieve a plasma AT III activity >120% during a 14 day study period (n = 14, AT III group). Plasma concentrations of interleukin (IL)-6 and IL-8 and of the circulating soluble adhesion molecules sICAM-1 and sE-selectin, as well as of PMN elastase, were determined daily. Additionally, total leukocyte count and C-reactive protein (CRP) were measured daily, and body temperature was registered. Compared to control patients, a down-regulation of plasma IL-6 was observed in the AT III group (p < or = .01). AT III supplementation prevented the continuous increase in sICAM-1 plasma concentration observed in control patients and led to a significant fall in soluble sE-selectin and CRP concentration (p < or = .01). This fall corresponded to a down-regulation of body temperature over time (p < or = .01). There was no AT III effect on IL-8, PMN-elastase concentration, or total leukocyte count. Our results show that long-term AT III supplementation attenuates the systemic inflammatory response in patients with severe sepsis. The down-regulation of IL-6 may also explain the fall in endothelium-derived adhesion molecules and may represent the molecular basis by which AT III exerts its beneficial effects on organ function.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; C-Reactive Protein; Critical Care; E-Selectin; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Sepsis

Approximately half of patients who undergo cardiac surgery develop systemic inflammatory response syndrome. Extracorporeal circulation and intestinal injury may play a role in this inflammatory response, although their relative contributions remain elusive. Moreover, it is largely unknown to what extent these factors contribute to cardiac surgery-induced postoperative organ dysfunction.. In this secondary analysis, we measured circulating levels of the intestinal damage marker intestinal fatty acid binding protein (I-FABP) and of the inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, IL-1RA, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β in 180 patients undergoing on-pump cardiac surgery. The average Z-score of levels of the different cytokines was used as an integral measure of the cytokine response. Relationships between duration of extracorporeal circulation, extent of intestinal injury, inflammation, and postoperative organ dysfunction were explored.. Plasma I-FABP levels increased during surgery, with peak levels observed at the end of cardiopulmonary bypass (CPB). Except for TNF-α, the levels of all cytokines increased during surgery, with peak levels observed either 2 (MCP-1, MIP-1α, and MIP-1β), 4 (IL-6, IL-8, and IL-1RA) or 6 (IL-10) hours after the end of CPB. While the duration of CPB significantly correlated with cytokine Z-score (r=0.544, p<0.05), no relationship with I-FABP levels was found. Furthermore, no significant correlations between I-FABP and cytokine levels were observed. The duration of CPB correlated with a deterioration in postoperative kidney function (estimated glomerular filtration rate [eGFR]) and troponin levels. Cytokine Z-score was associated with postoperative troponin levels, fluid administration, inotropic score, pulmonary alveolar-arterial gradient on the first postoperative morning, and deterioration of kidney function (eGFR). I-FABP levels did not correlate with any of the cardiovascular, pulmonary, or renal parameters.. In patients undergoing low-risk cardiac surgery, the duration of CPB represents an important determinant of the systemic cytokine response, whereas both the CPB duration and the systemic inflammatory response contribute to subsequent organ dysfunction. Intestinal damage does not appear to play a relevant role in the postoperative inflammatory response and development of postoperative organ dysfunction in these patients.

Topics: Adult; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Chemokine CCL4; Cytokines; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-6; Interleukin-8; Intestinal Diseases; Multiple Organ Failure; Tumor Necrosis Factor-alpha

Although early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.. We enrolled 129 children with infection into three groups: non-sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-α, and IFN-γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.. Significantly higher CRP, PCT, and IL-6 levels were detected in the Sepsis 1.0 than the non-sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL-6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL-8, and IL-10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL-8), and 0.860 (IL-10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.. In pediatric sepsis, combining any two of CRP, PCT, and IL-6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL-8, and IL-10.

Topics: Biomarkers; C-Reactive Protein; Child; Early Diagnosis; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Multiple Organ Failure; Procalcitonin; ROC Curve; Sepsis; Tumor Necrosis Factor-alpha

Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identification of those at risk of death and persistent organ dysfunctions is necessary to enrich patients for future trials of sepsis therapeutics. Here, we sought to integrate endothelial and PERSEVERE biomarkers to estimate the composite risk of death or organ dysfunctions on day 7 of septic shock.. We measured endothelial dysfunction markers from day 1 serum among those with existing PERSEVERE data. TreeNet® classification model was derived incorporating 22 clinical and biological variables to estimate risk. Based on relative variable importance, a simplified 6-biomarker model was developed thereafter.. Among 502 patients, 49 patients died before day 7 and 124 patients had persistence of MODS on day 7 of septic shock. Area under the receiver operator characteristic curve (AUROC) for the newly derived PERSEVEREnce model to predict death or day 7 MODS was 0.93 (0.91-0.95) with a summary AUROC of 0.80 (0.76-0.84) upon tenfold cross-validation. The simplified model, based on IL-8, HSP70, ICAM-1, Angpt2/Tie2, Angpt2/Angpt1, and Thrombomodulin, performed similarly. Interaction between variables-ICAM-1 with IL-8 and Thrombomodulin with Angpt2/Angpt1-contributed to the models' predictive capabilities. Model performance varied when estimating risk of individual organ dysfunctions with AUROCS ranging from 0.91 to 0.97 and 0.68 to 0.89 in training and test sets, respectively.. The newly derived PERSEVEREnce biomarker model reliably estimates risk of death or persistent organ dysfunctions on day 7 of septic shock. If validated, this tool can be used for prognostic enrichment in future pediatric trials of sepsis therapeutics.

Topics: Biomarkers; Child; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Multiple Organ Failure; Prognosis; Sepsis; Shock, Septic; Thrombomodulin

Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown.. We used the model of cecal ligation and puncture (CLP) to investigate the role of LXR activation during sepsis.. In this study, we verified that LXR activation reduces neutrophil chemotactic and killing abilities in vitro. Mice treated with LXR agonists showed higher sepsis-induced mortality, which could be associated with reduced neutrophil infiltration at the infectious foci, increased bacteremia, systemic inflammatory response, and multiorgan failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load, and multiorgan dysfunction. More important, neutrophils from septic patients showed increased ABCA1 messenger ribonucleic acid levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared with cells from healthy individuals.. Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.

Topics: Adult; Animals; ATP Binding Cassette Transporter 1; Cecum; Disease Models, Animal; Female; Humans; Inflammation; Interleukin-8; Ligation; Liver X Receptors; Male; Mice; Mice, Inbred C57BL; Middle Aged; Multiple Organ Failure; Neutrophil Infiltration; Neutrophils; Punctures; Sepsis

Translocation of bacteria across the intestinal barrier is important in the pathogenesis of systemic sepsis and multiple organ dysfunction syndromes. Inflammatory cytokines increase paracellular permeability that allows increased luminal bacteria to translocate across mucosal epithelium and further deteriorate the gut barrier. In order to reduce this risk, the prophylactic use of probiotics has been recently addressed. In this paper, we investigate the protective role toward tumour necrosis factor (TNF)-α induced non-pathogenic Escherichia coli translocation across Caco-2 monolayers of Lactobacillus strains. According to our experimental data, Lactobacillus plantarum L9 and Lactobacillus acidophilus LA have good capacities to adhere to Caco-2 cells. Addition of L. plantarum L9 and L. acidophilus LA to the enterocyte monolayer surface result in significant inhibition of E. coli adhesion and cell internalisation. However, L. plantarum L9 and L. acidophilus LA did not inhibit the growth of the non-pathogenic E. coli B5 after 24 h incubation. Exposure to TNF-α for 6 h caused a dramatic increase in E. coli B5 translocation across Caco-2 cells, which was uncoupled from increases in paracellular permeability. Pretreatment with L. plantarum L9 prevent TNF-α induced transcellular bacterial translocation and IL-8 production in Caco-2 cells. L. plantarum L9 also did not affect the integrity of the monolayers, as indicated by lactate dehydrogenase release, horseradish peroxidase permeability, and transepithelial electrical resistance. L. plantarum L9 showed the potential to protect enterocytes from an acute inflammatory response and therefore could be good potential prophylactic agents in counteracting bacterial translocation.

Topics: Bacterial Adhesion; Bacterial Translocation; Caco-2 Cells; Cell Line, Tumor; Escherichia coli; Humans; Inflammation; Interleukin-8; Intestinal Mucosa; Lactobacillus acidophilus; Lactobacillus plantarum; Multiple Organ Failure; Probiotics; Sepsis; Tumor Necrosis Factor-alpha

Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators.. We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat.. NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat.. UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.

Topics: Acinar Cells; Adult; Aged; Animals; Biomarkers; Cytokines; Fat Necrosis; Fatty Acids, Unsaturated; Female; Humans; Interleukin-1beta; Interleukin-8; Leukocytes, Mononuclear; Lipolysis; Male; Middle Aged; Multiple Organ Failure; Pancreas; Pancreatic Pseudocyst; Pancreatitis, Acute Necrotizing; Rats; Rats, Wistar; Severity of Illness Index

During septic shock, tumor necrosis factor alpha (TNFα) is an early response gene and induces a plethora of genes and signaling pathways. To identify robust signals in genes reliably upregulated by TNFα, we first measured microarray gene expression in vitro and searched methodologically comparable, publicly available data sets to identify concordant signals. Using tag single-nucleotide polymorphisms in the genes common to all data sets, we identified a genetic variant of the TNFAIP2 gene, rs8126, associated with decreased 28-day survival and increased organ dysfunction in an adult cohort in the Vasopressin and Septic Shock Trial. Similar to this cohort, we found that an association with rs8126 and increased organ dysfunction is replicated in a second cohort of septic shock patients in the St. Paul's Hospital Intensive Care Unit. We found that TNFAIP2 inhibits NF-x03BA;B activity, impacting the downstream cytokine interleukin (IL)-8. The minor G allele of TNFAIP2 rs8126 resulted in greater TNFAIP2 expression, decreased IL-8 production and was associated with decreased survival in patients experiencing septic shock. These data suggest that TNFAIP2 is a novel inhibitor of NF-x03BA;B that acts as an autoinhibitor of the TNFα response during septic shock.

Topics: Adult; Canada; Cytokines; Datasets as Topic; Genotyping Techniques; Humans; Immunity, Innate; Interleukin-8; Microarray Analysis; Multiple Organ Failure; NF-kappa B; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Shock, Septic; Signal Transduction; Survival Analysis; Tumor Necrosis Factor-alpha

The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF).. PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts.. Multiple PICUs in the United States.. Standard care.. PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase. PERSEVERE-II had an AUC of 0.89 (0.85-0.93) and performed equally well across TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly enrolled subjects. Sample size calculations for a clinical trial testing the efficacy of plasma exchange for children with septic shock and TAMOF indicated PERSEVERE-II-based stratification could substantially reduce the number of patients necessary, when compared with no stratification.. Testing PERSEVERE in the context of septic shock phenotypes prompted a revision incorporating platelet count. PERSEVERE-II performs well upon testing, independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a prognostic enrichment tool.

Topics: Biomarkers; Chemokine CCL3; Child; Child, Preschool; Female; Granzymes; HSP70 Heat-Shock Proteins; Humans; Infant; Intensive Care Units, Pediatric; Interleukin-8; Male; Matrix Metalloproteinase 8; Models, Statistical; Multiple Organ Failure; Platelet Count; Prognosis; Risk Assessment; Shock, Septic; Thrombocytopenia; United States

To evaluate the predictive value of 6 different biomarkers in the development of multiple-organ failure (MOF) and mortality in a contemporary prospective cohort of acute respiratory distress syndrome (ARDS).. Patients with ARDS admitted to a tertiary referral center during an 8-month period were included. Plasma sample collection of 6 different biomarkers on days 1, 3, and 5 after ARDS onset was performed (von Willebrand factor, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, interleukin 8, receptor for advanced glycation end-products, and club cell secretory protein). Main outcomes included hospital mortality and development of MOF. Logistic regression models for MOF and mortality prediction were created including biomarkers levels and clinical predictors.. One hundred patients were included in the study. Do-not-resuscitate status and McCabe score were independently associated with increased mortality. None of the 6 biomarkers measured at the time of ARDS diagnosis predicted hospital mortality. After adjustment for important clinical characteristics, elevated day-1 interleukin 8 levels were associated with the development of MOF.. Addition of biomarkers did not improve mortality prediction in this cohort of ARDS. Association between elevated interleukin 8 levels and progression of organ failures suggests an important role of exaggerated inflammatory response in the development of MOF.

Topics: Aged; Antithrombin III; APACHE; Biomarkers; Female; Hospital Mortality; Humans; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Peptide Hydrolases; Phospholipase A2 Inhibitors; Plasminogen Activator Inhibitor 1; Prospective Studies; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Respiratory Distress Syndrome; Resuscitation Orders; Uteroglobin; von Willebrand Factor

The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified.. Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53 MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA).. During MCS treatment, 32 patients experienced moderate MOFS (tSOFA < 11; A group), while 21 patients experienced severe MOFS (tSOFA ≥ 11) with favorable (B group) or adverse (n = 13, C group) outcomes. At preimplant, higher values of left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were the only parameter independently associated with A group. In C group, during the first postoperative week, high levels of interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α, and an increase of neopterin and adhesion molecules, precede tSOFA worsening and exitus.. The MCS patients of C group show an excessive release to IL-8 and TNF-α, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS.

Topics: Adult; Aged; Cell Adhesion Molecules; Glomerular Filtration Rate; Heart Failure; Heart-Assist Devices; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Middle Aged; Multiple Organ Failure; Neopterin; Tumor Necrosis Factor-alpha; Young Adult

We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP).. Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor α were measured on admission and at days 1, 2, and 14 in 60 patients admitted with first attack of AP. The prediction of single-organ and multiorgan failure from the cytokine profiles was evaluated by receiver operating characteristic analyses.. Interleukin 6 and IL-8 levels were significantly higher in patients who developed renal, respiratory, and circulatory failure, as was the case for patients with multiorgan failure. Interleukin 18 levels were significantly elevated in renal and respiratory failure only. Tumor necrosis factor α was significantly elevated in all types of organ failures, except for intestinal failure.. Synchronous measurements of 4 cytokines demonstrated IL-6 and IL-8 to be predictive as early surrogate markers with regard to organ failures in AP. The fact that all of the cytokines were particularly elevated in patients with organ failures calls for evaluation of agents modifying the severe inflammatory response in patients with AP.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cytokines; Denmark; Female; Humans; Inflammation Mediators; Interleukin-18; Interleukin-6; Interleukin-8; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Predictive Value of Tests; Prospective Studies; ROC Curve; Systemic Inflammatory Response Syndrome; Time Factors; Tumor Necrosis Factor-alpha; Young Adult

Cytokines are central mediators of the immune-inflammatory response to injury and subsequent multiple organ dysfunction syndrome (MODS). Although previous studies evaluated cytokine levels after trauma, differences between patients with burn and non-burn trauma have not been assessed systematically.. A prospective database of trauma patients admitted between May 2004 and September 2007 to the burn or surgical intensive care units within 24 h of injury with an anticipated stay of at least 72 h was analyzed. Sequential clinical and laboratory parameters were collected in the first week, including multiplex analysis data for plasma levels of inflammatory cytokines (IL-6, and IL-8). Patients with known pre-injury coagulopathy were excluded. A Marshall score of 10 or greater was defined as MODS.. A total of 179 patients were enrolled (67 burn and 112 non-burn). Plasma IL-6 and IL-8 levels were markedly elevated in both burn and non-burn patients compared to healthy volunteers. Burn subjects had higher levels of IL-6 and IL-8 than the non-burn on days 1 through 7 after injury. Subjects with burns and at least 30% total body surface area were older and had a lower injury severity score, a higher prevalence of MODS, and correspondingly higher mortality. Multivariate analysis of injury type, MODS, and time did not demonstrate an influence of MODS.. Burns were associated with a greater and more sustained immune-inflammatory response than non-burn trauma as evidenced by elevated plasma IL-6 and IL-8 levels during the first week. There was no association between MODS and plasma cytokine levels.

Topics: Adult; Burns; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Prospective Studies; Systemic Inflammatory Response Syndrome; Wounds and Injuries

Fibroblast migration is an initiating step in fibroproliferation; its involvement during acute lung injury and acute respiratory distress syndrome remains poorly understood. The aims of this study were: 1) to determine whether bronchoalveolar lavage fluids from patients with acute lung injury/acute respiratory distress syndrome modulate lung fibroblast migration; 2) to assess lung fibroblast migration's clinical relevance; and 3) to evaluate the role of the platelet-derived growth factor pathway in this effect.. Prospective cohort study.. Three intensive care units of a large tertiary referral center.. Ninety-three ventilated patients requiring bronchoalveolar lavage fluids were enrolled (48 with acute respiratory distress syndrome, 33 with acute lung injury, and 12 ventilated patients without acute lung injury/acute respiratory distress syndrome).. After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28 days and clinical outcomes were recorded. Migration assays were performed by using a Transwell model; bronchoalveolar lavage fluids platelet-derived growth factor and soluble platelet-derived growth factor receptor-α were characterized by Western blot and measured by ELISA.. Most of the bronchoalveolar lavage fluids inhibited basal fibroblast migration. Bronchoalveolar lavage fluids chemotactic index increased with severity of lung injury (28% in patients without acute lung injury/acute respiratory distress syndrome and with acute lung injury vs. 91% in acute respiratory distress syndrome patients; p = .016). In acute lung injury/acute respiratory distress syndrome patients, inhibition of basal fibroblast migration by bronchoalveolar lavage fluids below 52% was independently associated with a lower 28-day mortality (odds ratio [95% confidence interval] 0.313 [0.10-0.98], p = .046). Platelet-derived growth factor-related peptides and soluble platelet-derived growth factor-Rα were detected in all bronchoalveolar lavage fluids from acute lung injury/acute respiratory distress syndrome patients. The effect of bronchoalveolar lavage fluids stimulating migration was inhibited by a specific platelet-derived growth factor receptor inhibitor (AG1296). Bronchoalveolar lavage fluids inhibiting migration reversed the effect of rh-platelet-derived growth factor-BB and reduced by 40% the binding of 125I-platelet-derived growth factor-BB to fibroblast cell surface in favor of a role for platelet-derived growth factor-sRα.. : Together, our results suggest that during acute lung injury, fibroblast migration is modulated by bronchoalveolar lavage fluids through a platelet-derived growth factor/platelet-derived growth factor-sRα balance. Migration is associated with clinical severity and patient 28-day mortality.

Topics: Acute Lung Injury; Aged; Blotting, Western; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cell Line; Cell Movement; Enzyme Inhibitors; Female; Fibroblasts; Humans; Intensive Care Units; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Neutrophils; Platelet-Derived Growth Factor; Prospective Studies; Receptors, Platelet-Derived Growth Factor; Respiration, Artificial; Respiratory Distress Syndrome; Severity of Illness Index; Tyrphostins

Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-α, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.

Topics: Asian People; Genotype; Haplotypes; Humans; Interleukin-10; Interleukin-8; Multiple Organ Failure; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Prospective Studies; Sepsis; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha; Wounds and Injuries

Posttrauma apoptosis resistance of neutrophils (PMN) is related to overshooting immune responses, systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Recently, we have shown that the apoptosis resistance in circulating PMN from severely injured patients which is known to be mediated by high serum levels of pro-inflammatory cytokines can be overcome by the activation of Fas death receptor. Here, we aimed to study whether stimulation of surface Fas leads to the inactivation of hyperactivated PMN from critically ill patients with SIRS. PMN from 23 multiple trauma patients (mean injury severity score (ISS) 34±1.9) were isolated at day 1 after admission to the trauma center. PMN from 17 volunteer blood donors served as controls. Neutrophil activity has been determined after ex vivo short (1 h) and long-term (4 h) stimulation of freshly isolated PMN with immobilized agonistic anti-Fas antibodies. We found neutrophil chemotactic migration in response to IL-8, phagocytosis and oxidative burst to be significantly inhibited in control cells already after short-term (1 h) Fas stimulation. In contrast, inactivation of trauma PMN by agonistic anti-Fas antibodies was found to be efficient only after long-term (4 h) incubation of cells with agonistic antibodies. Thus, in trauma PMN down-regulation of neutrophil activity seems to be delayed when compared to cells isolated from healthy controls, suggesting impaired susceptibility for Fas stimulation in these cells. Interestingly, whereas Fas-mediated inhibition of phagocytosis and oxidative burst could be prevented by the broad range caspase inhibitor t-butoxycarbonyl-aspartyl(O-methyl)-fluoromethyl ketone (BocD-fmk), the chemotactic activity in response to IL-8 was unaffected. In conclusion, we demonstrate that stimulation of neutrophil Fas does not only initiate apoptosis but also induces inhibition of neutrophil functions, partially by non-apoptotic signaling.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis; Chemotaxis, Leukocyte; Fas Ligand Protein; fas Receptor; Female; Flow Cytometry; Humans; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Neutrophils; Phagocytosis; Respiratory Burst; Signal Transduction; Systemic Inflammatory Response Syndrome; Wounds and Injuries

The infiltration of 'primed' polymorphonuclear neutrophils into multiple organs has been reported in cases of traumatic or hemorrhagic shock. Since multiple injuries are usually observed in cases of physical abuse of the elderly, we investigated neutrophil infiltration into the heart, lung, liver and kidney in cases of abused elderly individuals using immunohistochemistry for myeloperoxidase (MPO). In addition, we examined the expression of molecules associated with neutrophil infiltration, including P-selectin as the adhesion molecule and IL-8 as the chemotactic factor. The number of neutrophils in the physically abused elder cases was increased significantly, particularly in the lung and liver, compared with that of control cases of sharp instrument injury, single fatal blunt injury and polytrauma. In addition, P-selection expression in the endothelium and the presence of IL-8-positive cells (mainly macrophages) in the lung and liver of abuse cases were significantly greater than those in control cases. In contrast, the number of MPO-, P-selectin- and IL-8-positive cells in cases of multiple organ failure (MOF) due to various causes was significantly greater than that in abuse cases. It is known that primed neutrophils accumulation may undergo MOF by 'activation' due to secondary insults. Thus, our results suggest that MPO immunostaining can distinguish cases of elderly physical abuse from non-abuse and MOF cases. In addition, our results indicate that MPO is a potential diagnostic marker for elder physical abuse, and that P-selectin and IL-8 may be useful for a more accurate diagnosis. Finally, our results also suggest that elder cases of physical abuse may be in a primed stage of MOF, and are at risk of falling into MOF by various secondary insults including those following abuse.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Elder Abuse; Endothelial Cells; Endothelium; Female; Forensic Pathology; Humans; Immunohistochemistry; Injury Severity Score; Interleukin-8; Kidney; Liver; Lung; Macrophages; Male; Multiple Organ Failure; Myocardium; Neutrophils; P-Selectin; Peroxidase

To observe the differences in the cytokine levels in the serum and ascites caused by Gram-positive or Gram-negative bacterial infection in patients with multiple organ dysfunction syndrome (MODS).. The cytokines in the serum and ascites of the patients were examined by enzyme-linked immunosorbent assay in 27 patients with MODS due to Gram-positive (n=13) or Gram-negative (n=14) bacterial infection at day 1.. The levels of LPS and TNF-a were higher in the patients with Gram-negative bacterial infection than in patients with Gram-positive infection (P<0.05), but the levels of IL-6, IL-8 and IL-10 remained comparable between the two groups (P>0.05).. Testing of LPS and TNF-a in the serum and ascites of patients with MODS caused by Gram-positive or -negative bacterial infection may help to identify the pathogens for peritonitis resulting in MODS.

Topics: Ascites; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Multiple Organ Failure; Serum; Tumor Necrosis Factor-alpha

Severe trauma may induce alternations of cytokine response and polymorphonuclear cell (PMN) activity in patients. This study investigated the correlation of plasma migration inhibitory factor (MIF) level and PMN activation after severe injury, and their relationship with clinical outcomes.. A prospective observational study was performed at the emergency department and intensive care unit of a university hospital. Thirty-two severe blunt trauma patients (Injury Severity Score greater than 16) with systemic inflammatory response syndrome (SIRS) were enrolled. Age- and gender-matched healthy persons were the controls. Patient blood samples were obtained within 24 hours of and at 72 hours after injury. PMNs were isolated and measured for NF-kBp65 translocation and respiratory burst. Plasma MIF, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 concentrations were measured. Control PMNs were incubated with patient plasma preincubated with anti-MIF antibody or anti-IL-6 antibody; cytokine blockade effects were evaluated.. Twelve patients developed organ failure. Compared with patients without organ failure, patients with organ failure had lower blood pressure and a higher base deficit on admission, higher NF-kBp65 translocation and respiratory burst of PMNs, and higher plasma MIF (968 ± 246 pg/mL vs 564 ± 299 pg/mL) and IL-6 (202 ± 91 pg/mL vs 119 ± 84 pg/mL) levels within 24 hours after injury. Plasma MIF had significant positive correlation with NF-kB translocation of PMNs within 24 hours of incurring trauma (R = 0.668). The presence of anti-MIF antibody in patients' plasma obtained within 24 hours, but not at 72 hours, after injury could significantly partially block the NF-kBp65 translocation and respiratory activity of PMNs in the controls.. An early increase of plasma MIF associates with NF-kB translocation and respiratory burst in PMNs of severe trauma patients and correlates with higher morbidity. MIF is one of the important factors responsible for early PMN activation and may provide a target of immunomodulation after injury.

Topics: Adult; Case-Control Studies; Confounding Factors, Epidemiologic; Female; Humans; Injury Severity Score; Interleukin-10; Interleukin-6; Interleukin-8; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Morbidity; Multiple Organ Failure; Neutrophils; NF-kappa B; Prospective Studies; Research Design; Respiratory Burst; Time Factors; Translocation, Genetic; Tumor Necrosis Factor-alpha; Wounds and Injuries

To explore the characteristics of immune imbalance in patients with multiple organ dysfunction syndrome (MODS) induced by severe intra-abdominal infection and its relationship with changing of TCM sthenia-asthenia syndrome.. Forty-six patients with MODS induced by severe intra-abdominal infection and treated with etiological and syndrome differentiation of integrative medicine were observed in succession. Patients' peripheral blood levels of interleukin-6/interleukin-10 ratio (IL-6/IL-10), human leukocyte antigen DR site (HLA-DR), helper T lymphocyte1/2 ratio (Th1/Th2), and the regulatory T lymphocyte (Treg) were measured on the 1st, 3rd and 7th day of the research respectively. And the distribution laws of TCM syndrome types, sthenia (S), asthenia (A), and mingled sthenia/asthenia (M), in patients were observed as well.. IL-6/IL-10 ratio at all the testing time points showed insignificant difference in patients of types S and M, while in those of type A, it was more lowered on the 7th day than that on the 1st day. HLA-DR lowered to <30% on the 7th day in all patients of type A and showed significant difference to that on the 1st day (P <0.05), while HLA-DR <30% was not found in all patients of types S and M. Th1/Th2 ratio in patients of types S and A was insignificant different at the foremost 3 days, but lowered significantly on the 7th day, while in patients of type M, it was unchanged in all the 7 days of observation. Treg level was unchanged in the foremost 3 days in patients of types S and M, while in those of type A, it raised on the 3rd day, but no raising was found in the subsequent 4 days. Comparisons of various indexes detected at corresponding time points respectively among patients with various syndrome types showed that, for levels of IL-6/IL-8, HLA-DR, and Th1/Th2, the sequence was S>M>A; and for Treg, it was A>M>S.. In the pathological process of MODS induced by severe intra-abdominal infection, the index IL-6/IL-10, reflecting the balance of the pro-/anti-inflammatory cytokines and the indexes HLA-DR, Th1/Th2 and Treg reflecting the immune function, all can exactly reflect the TCM asthenia-sthenia syndrome types. The sequence in patients of various syndrome types for levels of IL-6/IL-10, HLA-DR and Th1/Th2, is S> M>A, but for Treg it is the inverse, as A>M>S.

Topics: Adolescent; Adult; Aged; Diagnosis, Differential; HLA-DR Antigens; Humans; Interleukin-6; Interleukin-8; Medicine, Chinese Traditional; Middle Aged; Multiple Organ Failure; Peritonitis; Sepsis; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells; Yang Deficiency; Young Adult

Severe tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. However, there is little known about the functional alterations of monocytes in the early posttraumatic phase, characterized by the battle of the individual with the initial trauma.. Thirteen patients with severe multiple injury; injury severity score (ISS) >16 points (17 to 57) were included. The cytokine synthesis profiles of monocytes were characterized on admission, and followed up 6, 12, 24, 48, and 72 hours after severe multiple injury using flow cytometry. Whole blood was challenged with lipopolysaccharide (LPS) and subsequently analyzed for intracellular monocyte-related TNF-alpha, IL-1beta, IL-6, and IL-8. The degree of organ dysfunction was assessed using the multiple organ dysfunction syndrome (MODS)-score of Marshall on admission, 24 hours and 72 hours after injury.. Our data clearly show that the capacity of circulating monocytes to produce these mediators de novo was significantly diminished very early reaching a nadir 24 hours after severe injury followed by a rapid and nearly complete recovery another 48 hours later compared with admission and controls, respectively. In contrast to the initial injury severity, there was a significant correlation detectable between the clinical signs of multiple organ dysfunction and the ex vivo cytokine response.. As our data derived from very narrow intervals of measurements, they might contribute to a more detailed understanding of the early immune alterations recognized after severe trauma. It can be concluded that indeed as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function. Moreover, our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is not only an in vitro phenomenon but also undistinguishable associated with the onset of organ dysfunction in the clinical scenario.

Topics: Adult; Case-Control Studies; Cytokines; Down-Regulation; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Male; Monocytes; Multiple Organ Failure; Multiple Trauma; Tumor Necrosis Factor-alpha

Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro- and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period.. 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6h, 12h, 24h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters.. Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35).. The current study presents an image of the serum Il-6, 8 and 10 releases in multiple trauma patients in the very early post-trauma period. We could thereby demonstrate that interleukin levels can clearly differentiate the presence of hemorrhagic shock and subsequent massive blood product substitution, the development of multiple organ failure and clinical outcome. No significant connection to age, gender and brain injury could be detected. Most importantly, changes in interleukin levels can be observed in the very early posttraumatic phase, at the earliest 90 minutes after trauma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Erythrocyte Transfusion; Female; Humans; Injury Severity Score; Interleukin-10; Interleukin-6; Interleukin-8; Luminescent Measurements; Male; Middle Aged; Multiple Organ Failure; Outcome Assessment, Health Care; Systemic Inflammatory Response Syndrome; Time Factors; Young Adult

To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (VC), low tidal volume (Vt), high positive end-expiratory pressure (PEEP) ventilation.. Prospective, randomized, laboratory animal study.. Twenty-seven male New Zealand white rabbits.. Anesthetized rabbits with hydrochloric acid-induced ALI were randomized (n = 9 per group) to 5.5 h NAVA (non-paralyzed), VC (paralyzed; Vt 6-ml/kg), or VC (paralyzed; Vt 15-ml/kg). PEEP was adjusted to hemodynamic goals in NAVA and VC6-ml/kg, and was 1 cmH2O in VC15-ml/kg.. PaO2/FiO2; lung wet-to-dry ratio; lung histology; interleukin-8 (IL-8) concentrations in broncho-alveolar-lavage (BAL) fluid, plasma, and non-pulmonary organs; plasminogen activator inhibitor type-1 and tissue factor in BAL fluid and plasma; non-pulmonary organ apoptosis rate; creatinine clearance; echocardiography. PEEP was similar in NAVA and VC6-ml/kg. During NAVA, Vt was lower (3.1 +/- 0.9 ml/kg), whereas PaO2/ FiO2, respiratory rate, and PaCO2 were higher compared to VC6-ml/kg (p<0.05 for all). Variables assessing ventilator-induced lung injury (VILI), IL-8 levels, non-pulmonary organ apoptosis rate, and kidney as well as cardiac performance were similar in NAVA compared to VC6-ml/kg. VILI and non-pulmonary organ dysfunction was attenuated in both groups compared to VC15-ml/kg.. In anesthetized rabbits with early experimental ALI, NAVA is as effective as VC6-ml/kg in preventing VILI, in attenuating excessive systemic and remote organ inflammation, and in preserving cardiac and kidney function.

Topics: Acute Lung Injury; Analysis of Variance; Animals; Bronchoalveolar Lavage Fluid; Diaphragm; Disease Models, Animal; Electrophysiological Phenomena; Feedback, Physiological; Interleukin-8; Male; Multiple Organ Failure; Plasminogen Activator Inhibitor 1; Positive-Pressure Respiration; Prospective Studies; Rabbits; Random Allocation; Respiration, Artificial; Statistics, Nonparametric; Thromboplastin; Tidal Volume; Ventilator-Induced Lung Injury

Based on the implication of soluble triggering receptor expressed on myeloid cells (sTREM-1) in the septic cascade, it was investigated whether it participates or not in posttraumatic systemic inflammatory response syndrome (SIRS).. Blood was sampled on days 1, 4, 7, and 15 from 69 patients with SIRS after multiple injuries and upon presentation of a septic complication. Concentrations of sTREM-1, tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8, and interferon-gamma were determined by an enzyme immunoassay. Samples drawn on day 1 from 10 trauma patients without SIRS served as controls.. In 26 patients with SIRS without septic complication, sTREM-1, TNFalpha, and IL-8 remained stable over follow-up; IL-6 decreased and interferon-gamma increased on days 4 and 7 compared with day 1. TNFalpha was the only variable being higher upon advent of septic shock compared with patients without SIRS and upon presentation of SIRS, sepsis, and severe sepsis (p of comparisons with all subgroups <0.0001). Mortality of patients with sTREM-1 greater than 180 pg/mL was 5.3% compared with 28.0% of those with sTREM-1 lower than 180 pg/mL (p 0.035). sTREM-1 higher than 40 pg/mL had sensitivity 56.5% and specificity 91.7% for the differential diagnosis between SIRS and sepsis after multiple injuries.. This is the first study providing evidence about the participation of sTREM-1 in posttraumatic SIRS. Its levels are increased and remain constant over time in patients who did not develop any complications whereas it seems to behave as an anti-inflammatory mediator.

Topics: Adult; Aged; Bacteremia; Cross Infection; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Gram-Negative Bacterial Infections; Humans; Injury Severity Score; Interferon-gamma; Interleukin-6; Interleukin-8; Male; Membrane Glycoproteins; Middle Aged; Multiple Organ Failure; Multiple Trauma; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Prospective Studies; Pyelonephritis; Receptors, Immunologic; Shock, Septic; Systemic Inflammatory Response Syndrome; Time Factors; Triggering Receptor Expressed on Myeloid Cells-1; Tumor Necrosis Factor-alpha

Systemic inflammation subsequent to polytrauma is connected to neutrophil (PMN) dysregulation characterized by reduced NF-kB-translocation and cytokine expression. The dynamics of NF-kB-activation as well as its down-stream regulation of IL-8-expression in PMN following major trauma remain unclear. The aim of this pilot study was to analyse NF-kB nuclear translocation in relation to IL- 8-mRNA-expression in PMN after major trauma.. PMN were isolated from blood samples of 15 major trauma patients (New Injury Severity Score, NISS > 16) drawn within 90 min and subsequently 6, 12, 24, 48, 72 h after trauma. NF-kB-translocation was analysed by Electrophoretic Mobility Shift Assay, EMSA and quantified by densitometry [arbitrary units], IL-8-mRNA-expression by RT-PCR, [copies/50 ng RNA]. Additionally, NF-kB-translocation and IL-8-expression in PMN of healthy volunteers were analysed natively (-control) and after LPS stimulation (+control).. NF-kB-translocation and IL-8-mRNA-expression was significantly increased in polytrauma patients (n=15; NISS: 34 +/- 8 [mean +/- SEM]) initially. In non-survivors, NFkB- translocation was significantly increased on admission and subsequently reduced within 6 h, while it increased in the survivors group. After 24 h, a second significant increase in NF-kB-activity and IL-8-expression was found in survivors that was subsequently reduced in both groups.. This pilot study has shown that a concomitant initial increase in transcriptional NF-kB-activity and IL-8 mRNA expression was observed in the early posttraumatic period which preceded the down-regulation of the innate immune system.

Topics: Adolescent; Adult; Aged; Female; Humans; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Neutrophils; NF-kappa B; Protein Transport; RNA, Messenger; Wounds and Injuries

An important and persistent laboratory finding has been that males and females respond differently after traumatic injury and hemorrhagic shock. We have previously presented clinical data showing that male gender is independently associated with a 40% higher rate of multiple organ failure (MOF) and a 25% higher rate of nosocomial infection (NI) after injury; however, the mechanism responsible for this dimorphic response after injury has not been adequately characterized clinically.. Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in severely injured adults with blunt hemorrhagic shock. Proteomic analysis of serum inflammatory cytokines, on days 0, 1, and 4 postinjury, was performed on 46 males and 34 females. Repeated measures ANOVA were used to compare serial IL-1beta, TNF-alpha, IL-6, IL-8, and IL-10 serum levels across gender, while controlling for important confounders. Logistic regression modeling was then used to analyze the independent risk of MOF and NI associated with gender.. IL-6 serum levels were statistically higher in males relative to females (p = 0.008). This higher level of IL-6 expression in males remained statistically significant over time even after controlling for differences in age, initial base deficit, ISS, and 12-hour blood transfusion requirements (p = 0.025). No differences in IL-1beta serum levels (p = 0.543), TNF-alpha, (p = 0.200) IL-8 (p = 0.107), and IL-10 (p = 0.157) were found. Males had a higher crude incidence of MOF and an 11-fold higher independent risk of MOF.. Persistently elevated IL-6 levels in males are associated with a higher rate of MOF. It is not known if this excessive IL-6 expression in males is causal or only a marker for poor outcome. Further studies are required to elucidate if this early, persistent IL-6 expression is responsible for the gender-based differential outcomes after injury.

Topics: Adult; Analysis of Variance; APACHE; Cross Infection; Humans; Injury Severity Score; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Length of Stay; Male; Multiple Organ Failure; Prospective Studies; Risk Factors; Sex Factors; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha; Wounds, Nonpenetrating

To explore the serum cytokine fluctuation in those adult patients with multiple organ dysfunction syndrome (MODS) during the post-operation stage of orthotopic liver transplantation (OLT) to guide the clinical treatment.. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8 and IL-10 were determined in 53 MODS patients who had received OLT. They were divided into two groups as control group and experimental group, according to whether continuous blood purification (CBP) had been performed or not. The levels of serum cytokines and intensive care unit (ICU) stay time, intubation time, mortality and ICU expenses were compared between the two groups.. The levels of serum TNF-alpha, IL-6 and IL-8 rose, while that of IL-10 increased dramatically compared with normal values (all P<0.05). After CBP, the serum levels of TNF-alpha, IL-6 and IL-8 all dropped to certain extent and became lower than those before the treatment (all P<0.05). IL-10's serum level was not changed compared with that before treatment. Those who received CBP stayed in the ICU for a longer period compared with control group, and the ICU expenses increased evidently with significant differences (P<0.05 or P<0.01). However, there was no difference in mortality between the two groups.. Under the effect of immunosuppressant in the post-OLT period, the excessive release of the anti-inflammatory mediators may become dominant leading to imbalance between proinflammatory and anti-inflammatory mediators leading to MODS. CBP may remove serum proinflammatory cytokines to act as an effective supportive treatment.

Topics: Adult; Aged; Cytokines; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Intraoperative Period; Liver Transplantation; Male; Middle Aged; Multiple Organ Failure; Tumor Necrosis Factor-alpha

Secondary abdominal compartment syndrome (ACS) is a lethal complication after resuscitation from burn shock, even after abdominal decompression (AD) is performed. This study investigated increased susceptibility to multiple organ dysfunction syndrome (MODS) in extensively burned patients with ACS.. Patients admitted to our burn unit between 2002 and 2005 with burns affecting 40% or more of the total body surface area without severe inhalation injury were analyzed. Hemodynamic parameters, blood gas analysis, and intrabladder pressure as intra-abdominal pressure were recorded. Serum interleukin (IL)-8 and IL-6 concentrations were measured in 20 of these patients. Lung injury score and Sequential Organ Failure Assessment scores were serially determined.. Fourteen of 38 patients developed intra-abdominal hypertension in 22.9 +/- 8.9 hours postburn. Hemodynamic parameters in these 14 patients, including peak intra-abdominal pressure (46.6 +/- 11.2 to 19.8 +/- 9.9 cm H2O), peak inspiratory pressure (51.4 +/- 10.5 to 31.8 +/- 7.0 cm H2O), and abdominal perfusion pressure (51.3 +/- 18.3 to 73.9 +/- 13.6 mm Hg), were improved immediately after AD. Despite AD, lung injury score and Sequential Organ Failure Assessment scores increased significantly 2 and 3 days postburn in patients who required AD. Plasma concentration of IL-8 was elevated in intra-abdominal hypertension patients 3 days postburn.. Intra-abdominal hypertension induced acute lung injury and MODS with IL-8 elevation, even though AD improved hemodynamic parameters in extensively burned patients.

Topics: Abdominal Cavity; Burns; Compartment Syndromes; Decompression, Surgical; Humans; Interleukin-8; Multiple Organ Failure; Respiratory Distress Syndrome

Although multiple organ failure (MOF) remains the leading cause of death after trauma, the pathogenic cellular and molecular mechanisms underlying MOF are poorly understood. In addition to proinflammatory and anti-inflammatory mediator cascades, the temporal onset of MOF has generated recent interest because the organ systems involved into MOF seem to deteriorate in a time-dependent fashion after trauma. We therefore investigated the temporal course of MOF in traumatized human patients and evaluated and compared the distribution patterns of cytokine expression, including interleukin (IL) 6, IL-8, IL-10, and the soluble tumor necrosis factor-[alpha] receptors sTNF-R p55 and sTNF-R p75 in early-onset versus late-onset MOF. In addition, we analyzed the predictive value of cytokine biomarkers of MOF and lethal outcome. In a prospective observational cohort study conducted at three trauma centers, all patients (n = 352) admitted to two level 1 trauma centers in Germany were enrolled in the study based on the following inclusion criteria: severe traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) score of 8 or lower and/or distinct changes in cranial computed tomography and/or multiple injuries (MT) to the body (at least two regions had Abbreviated Injury Scale score of 3 or higher). The incidence of MOF was evaluated using the modified Goris-MOF score. The temporal onset of MOF was divided into early-onset MOF (EMOF, developing on days 0-3), late-onset MOF (LMOF, developing on days 4-10), combined early-onset and late-onset MOF (CMOF), and patients never showing signs of MOF during the observation period. In addition, the levels of the serum cytokine markers IL-6, IL-8, IL-10, sTNF-R p55, and sTNF-R p75 were analyzed at specific posttraumatic time points using established enzyme-linked immunosorbent assay techniques. A total of 352 patients (274 men and 78 women; TBI, 101; TBI + MT, 125; MT, 126) were enrolled into the study. Patients assigned to the EMOF group showed specific disruption of pulmonary and cardiocirculatory function, whereas LMOF was significantly associated with hepatic failure. The patients without signs of MOF and the EMOF patients had the same risk of lethal outcome (8.2% vs. 7.5%); LMOF and CMOF were found to be associated with a 3- to 4-fold increase in mortality (38.5% vs. 30.6%, respectively). Analysis of cytokine serum biomarkers revealed that patients with LMOF showed a biphasic elevation of IL-6 and significantly higher sTNF-

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Injury Severity Score; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Receptors, Tumor Necrosis Factor, Type I; Survival Rate; Time Factors; Trauma Severity Indices; Tumor Necrosis Factor Decoy Receptors; Wounds and Injuries

Humoral mediators are potentially involved in the pathogenesis of postoperative complications following surgery. The aim of the present study is to evaluate the postoperative responses of circulating cytokines, chemokines, and stress hormones following liver resection, and their effects on postoperative infectious complications and organ dysfunction.. Perioperative plasma concentrations of interleukin (IL)-6, IL-10, IL-4, IL-8, macrophage chemoattractant protein (MCP)-1, cortisol, macrophage migration inhibitory factor (MIF), and leptin were measured by immunoassays in 128 consecutive patients undergoing liver resection.. Forty-three patients had postoperative infection and 11 had infection-related organ dysfunction. Plasma levels of all mediators except for IL-4 increased postoperatively. Postoperative levels of IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin were significantly higher in patients with organ dysfunction than in those without organ dysfunction (P < 0.05). However, postoperative MIF levels were not affected by postoperative infection or organ dysfunction. Plasma levels of IL-6, IL-10, IL-8, and MCP-1 were positively correlated with operation time (P < 0.0001) or blood loss (P < 0.0001), and higher in patients with jaundiced liver (P < 0.05). In univariate logistic regression analyses, elevated IL-6, IL-10, IL-8, and MCP-1, advanced age, large volume of blood loss, long operation time, long hepatic ischemia time, and major liver resection were significantly correlated with postoperative infection (P < 0.05). In multivariate analyses, IL-6 and IL-10 were significant predisposing factors for postoperative infection (P < 0.05), and blood loss and IL-6 for organ dysfunction (P < 0.01).. These results suggest that IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin are released after liver resection in response to surgical stress and correlated with postoperative infection and organ dysfunction, and that of these circulating mediators, IL-6 and IL-10, have a close relationship to the complications.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chemokine CCL2; Cytokines; Female; Humans; Hydrocortisone; Infections; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Leptin; Linear Models; Liver Diseases; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Stress, Physiological; Treatment Outcome

In experimental settings, the increased intestinal permeability (IP) following severe trauma is associated with increased serum concentrations of cytokines. Multiply injured patients are susceptible to the development of multiple organ failure (MOF). The aim of this study was to determine if altered IP after trauma was associated with upregulation of cytokines and if cytokines and IP influenced the development of MOF. In 30 multiply injured patients, IP was measured on days 2 and 4 after injury using the lactulose-mannitol (L-M) test, and the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 were determined simultaneously. The L-M ratio increased significantly from 0.049 (0.017-0.133) on day 2 to 0.150 (0.059-0.339) on day 4 (p < 0.02) On day 4, a significant correlation was also found between the L-M ratio and IL-6 (r = 0.43, p < 0.03). The IL-6 level on days 2 and 4 was significantly (p < 0.01 and p < 0.03, respectively) higher in MOF patients than in those without MOF, as was the TNF-alpha level on day 4 significantly higher (p < 0.04) in MOF patients. IP increases following multiple trauma, and on day 4 it correlates with the IL-6 level. However, in patients who develop MOF only cytokines are invariably increased, with IL-6 alone being significantly increased on both measurements in these patients.

Topics: Adult; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Intestinal Mucosa; Lactulose; Male; Mannitol; Middle Aged; Multiple Organ Failure; Permeability; Tumor Necrosis Factor-alpha; Wounds and Injuries

To investigate the effect of CVVH on the plasma levels of TNF-alpha, IL-1, IL-6, IL-8 in patients with multiple organ dysfunction syndrome (MODS).. Twenty-two patients with MODS were treated with continuous veno-venous hemofiltration (CVVH), venous and arterial blood samples were taken at 0, 1, 4, 8 hour following CVVH and ultrafiltration fluid samples were taken at 8 hour following CVVH. Arterial blood samples were used for blood gas analysis, venous blood samples and ultrafiltration fluid were used to measure the levels of cytokines by ELISA.. The plasma levels of TNF-alpha and IL-1 were significantly decreased following CVVH (P < 0.05). The IL-1, IL-6, IL-8 were detected in the ultrafiltration fluid and TNF-alpha was not. Heart rate decreased and mean arterial pressure (MAP) increased significantly 4 hrs after CVVH (P < 0.05). PaO(2)/FiO(2) increased significantly (P < 0.05). The APACHE II scores reduced after CVVH (P < 0.05). The reduction of APACHE II score and the elimination of cytokines were positively correlated with ultrafiltration flow rates. CVVH can remove some cytokines in plasma, reduce APACHEII score and improve hemodynamics and oxygenation in MODS. Moreover, higher volume hemofiltration has better effect on the elimination of cytokines and can further improve the prognosis of MODS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cytokines; Female; Hemofiltration; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Retrospective Studies; Tumor Necrosis Factor-alpha

Topics: Acetylcysteine; Critical Care; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Multiple Organ Failure; NF-kappa B; Randomized Controlled Trials as Topic; Systemic Inflammatory Response Syndrome; Treatment Failure

Red blood cell (pRBC) transfusion is an independent risk factor for multiple organ failure (MOF); a maladaptive immuno-inflammatory response is implicated. Interleukin-8 (IL-8) is one putative mediator of this response. We previously observed that injured patients resuscitated with pRBCs have increased plasma IL-8 compared with those given human polymerized hemoglobin (PolyHb). To further elucidate the mechanisms responsible for this difference in IL-8, we devised an ex-vivo transfusion model. We hypothesize that pRBC transfusion induces increased IL-8 gene expression that is avoided by the use of PolyHb.. Human volunteer blood was incubated alone (RB) or with a major transfusion (50% exchange) of either post-storage leukoreduced O-pRBCs (RB + pRBC) or PolyHb (RB + PolyHb) for 30 minutes at 37 degrees C. Total leukocyte (TL) or polymorphonuclear leukocyte (PMN) total RNA was isolated and IL-8 mRNA quantified. Results are reported as amol IL-8 mRNA/microg total RNA +/- SEM. Stats: ANOVA with Bonferroni/Dunn post hoc analysis.. Simulated transfusion of pRBCs increased TL IL-8 mRNA (RB=0.28 +/- 0.10 amol/microg total RNA, RB + pRBC=2.24 +/- 0.25 amol/microg total RNA, p <0.01), whereas PolyHb did not (B + PolyHb=0.82 +/- 0.30 amol/microg total RNA). PolyHb IL-8 mRNA was less than pRBC transfused (p <0.01). In PMNs, simulated transfusion of pRBCs increase IL-8 mRNA (RB=3.17 +/- 1.05 amol/microg total RNA, RB + pRBC=7.60 +/- 1.79 amol/microg total RNA, p <0.01), whereas PolyHb did not (RB + PolyHb=4.53 +/- 1.64 amol/microg total RNA).. Stored pRBCs induces increased TL and PMN IL-8 gene expression, whereas human polymerized hemoglobin, in lieu or pRBCs, avoids this increase. These experimental results corroborate our previous clinical studies and further encourage the study of PolyHb as a resuscitation strategy to decrease postinjury MOF.

Topics: Analysis of Variance; Blood Substitutes; Cells, Cultured; Erythrocyte Transfusion; Gene Expression Regulation; Graft Rejection; Hemoglobins; Humans; Interleukin-8; Leukocytes; Multiple Organ Failure; Neutrophils; Probability; Risk Factors; RNA; Sampling Studies; Sensitivity and Specificity

Aim of the study was to characterize different functions of circulating and emigrated, intra-abdominal polymorphonuclear leukocytes (cPMNs, ePMNs) during human secondary peritonitis.. In patients (n=25) with diffuse secondary peritonitis circulating and emigrated PMNs were characterized intra- and until 96 h postoperatively. Patients were allocated to two different groups, e. g. patients with septic complications (shock, organ failure, n=11) and patients without complications (n=14) during peritonitis. In addition a control group of patients (n=10) with abdominal surgery but without peritonitis was investigated. The lucigenin- and luminol-enhanced chemiluminescence was used to determine extra- and intracellular oxygen radical generation of PMNs. Besides spontaneous oxygen radical generation of PMNs, stimulated radical production was investigated after the addition of ionophores A23 187 and C3-coated zymosan. Phagocytosis by PMNs was characterized with opsonized E. coli bacteria and fluorescence-activated cell analysis.. Especially patients with complicated peritonitis had strong and long-lasting changes of PMNs functions. The toxic and tissue-destroying production of extracellular oxygen radicals by circulating PMNs was enhanced (e. g., A23 187 - stimulated oxygen radical generation 433 +/- 89 cpm/cPMNs (peritonitis with complications) versus 90 +/- 30 cpm/cPMNs (peritonitis without complications) versus 110 +/- 44 cpm/cPMNs (controls), p < 0.05). Phagocytosis (58 +/- 9 % (ePMNs, peritonitis with complications) versus 81 +/- 6 % (ePMNs, peritonitis without complications) versus 82.2 +/- 1.6 % (ePMNs, controls), p < 0.05) and phagocytosis-associated intracellular oxygen radical generation (8.23 +/- 1.6 x 10(3) cpm/ePMNs (peritonitis with complications) versus 25.2 +/- 5.2 x 10(3) cpm/ePMNs (peritonitis without complications) versus 11.7 +/- 2.8 cpm x 10(3) cpm/ePMNs (controls) p < 0.05) were suppressed.. Not for all patients with peritonitis does it seem favourable to modulate PMNs-functions. If immunomodulation would be able to down-regulate exaggerated functions of circulating PMNs and to up-regulate the suppressed functions of emigrated PMNs patients with complicated peritonitis might benefit from this therapy.

Topics: Colectomy; Free Radicals; Gastrectomy; Humans; Interleukin-8; Luminescent Measurements; Multiple Organ Failure; Neutrophils; Peritoneum; Peritonitis; Postoperative Complications; Prognosis; Reactive Oxygen Species; Shock, Septic; Tumor Necrosis Factor-alpha

Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-alpha(1)-antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.

Topics: Adult; Aged; alpha 1-Antitrypsin; Biomarkers; Complement Activation; Complement C1 Inactivator Proteins; Complement C1 Inhibitor Protein; Cytokines; Female; Humans; Interleukin-8; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Multiple Organ Failure; Neutrophils; Sepsis; Serpins; Shock, Septic

To evaluate the effectiveness and mechanisms of molecular adsorbents recirculating system (MARS) treatment in severe liver failure patients with multiple organ dysfunction syndrome (MODS).. 60 single MARS treatments were performed for 6 - 24 hours on 24 severe liver failure patients with MODS.. MARS therapy was associated with marked reduction of albumin bound toxins and water soluble toxins, together with a significant removal of NO and certain cytokines, such as TNF-alpha, IL-6, IL-8, and INF-gamma. These were associated with a improvement of the patients' clinical conditions including hepatic encephalopathy, deranged hemodynamic situation, as well as renal and respiratory function, thus resulted into marked decrease of sequential organ failure assessment (SOFA) score (from 9.72+-1.89 to 6.98+-2.34), and improving outcome: 9 patients were able to be discharged from the hospital or bridged to successful liver transplantation. The overall survival rate of 24 patients was 37.5%.. There is positive therapeutic impact and safety to use MARS on liver failure patients with MODS. The effectiveness of MARS is correlated with reducing the levels of NO and cytokines, except for completely removing of accumulated toxins in liver failure patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bioreactors; Female; Humans; Interferon-gamma; Interleukin-6; Interleukin-8; Liver Failure, Acute; Liver, Artificial; Male; Middle Aged; Multiple Organ Failure; Nitric Oxide; Sorption Detoxification; Tumor Necrosis Factor-alpha

Molecular Adsorbents Recirculating System (MARS) is a new promising artificial liver support therapy, the aim of this study was to assess the effectiveness of MARS to remove nitrous oxide (NO) and cytokines in severe liver failure patients with multiple organ dysfunction syndrome (MODS).. Sixty single MARS treatments were performed with length of 6-24 h on 24 severe liver failure patients (18 males/6 females) with MODS.. The MARS therapy was associated with a significant removal of NO and certain cytokines such as TNF-alpha, IL-6, IL-8, and INF-gamma, together with marked reduction of other non-water-soluble albumin bound toxins and water-soluble toxins, these were associated with a improvement of the patients' clinical conditions including hepatic encephalopathy, deranged hemodynamic situation and as well as renal and respiratory function, thus resulted into marked decrease of Sequential Organ Failure Assessment (SOFA) score and improved outcome: nine patients were able to be discharged from the hospital or bridged to successful liver transplantation, the overall survival of 24 patients was 37.5%.. We can confirm the positive therapeutic impact and safety to use MARS on liver failure patients with MODS associated with elevated levels of NO and cytokines.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cytokines; Female; Humans; Interferon-gamma; Interleukin-6; Interleukin-8; Liver Failure, Acute; Male; Middle Aged; Multiple Organ Failure; Nitrous Oxide; Renal Dialysis; Severity of Illness Index; Sorption Detoxification; Toxins, Biological; Tumor Necrosis Factor-alpha

Estimation of trauma severity currently relies on clinical diagnoses and scoring systems. However, the early estimation of the severity of chest trauma and overall soft tissue trauma (STT) remains insufficient. Traditional trauma scoring systems fail to reflect the individual trauma pattern and severity, neglecting the different outcomes after injuries in different body regions. Therefore, the aim of this prospective study was to detect laboratory markers that may reflect the pattern and extent of individual trauma in the very early phase after injury.. In 107 non-selected trauma patients, blood samples were collected almost immediately and then at short intervals after the trauma. In addition to the biochemical analysis of 20 different mediators viewed as potential trauma markers, the following data were correlated with the laboratory results: injury severity score (ISS), polytrauma score (PTS), Ulmer score HTAPE (trauma pattern specific: head (H), thorax (T), abdomen (A), pelvis (P), extremities (E); 0-3 degrees each), multiple organ failure score (MOF), overall, primary and secondary lethality.. ISS and the severity of head injury were clearly higher in non-survivors (n=17) than in survivors (n=90) (median ISS: 35 versus 18; median severity of head injury (H): 3 versus 1). Whereas head injury was correlated with early death (3 days post-trauma) was influenced by thoracic trauma (r=0.15) as well as by soft tissue trauma (STT, r=0.12). Of all investigated mediators, interleukin-6 (IL-6) displayed the highest correlations (r=0.66, P<0.00001) with the extent of chest trauma, followed by correlations with PTS, STT, fracture trauma (FT) and ISS during the first hour after trauma. There was no correlation between IL-6 and head injury. The extent of STT was correlated best to IL-8 (r=0.75), IL-6 (r=0.54), and creatine kinase (CK, r=0.49) plasma concentrations.. In the very early stage after an accident the severity of chest trauma is strongly correlated with the plasma concentration of IL-6, and the extent of overall soft tissue trauma (STT) to plasma concentrations of IL-8, IL-6, and CK.

Topics: Adolescent; Adult; Aged; Biomarkers; Craniocerebral Trauma; Creatine Kinase; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Soft Tissue Injuries; Statistics, Nonparametric; Survival Rate; Thoracic Injuries; Trauma Severity Indices; Wounds and Injuries

To explore the role of massive escharectomy at early postburn stage in the prevention of internal organ dysfunction.. (1) Ten cases of severely burned patients were randomly divided into early (A) and non-early escharectomy (B) groups in equal number. Venous blood samples were harvested from the patients of the two groups in 1, 3 and 7 postburn days (PBDs), And the samples from 6 healthy volunteers were taken as the control. The serum was separated from the above blood samples and was employed to stimulate cultured HUVECs in vitro. The cell viability and permeability was observed after the stimulation. (2) Seventy Wistar rats inflicted with 30% TBSA III degree scalding were used as an animal model, and were randomized into early (C, n = 30) and non-early escharectomy (D, n = 30) groups, with 5 normal rats as control in each group. Intra-peritoneal fluid infusion was carried out at 1, 3, 6, 12, 24 and 48 postburn hours (PBHs) in rats in both groups. The rats were killed by blood letting at 1 hour after fluid supplementation. The changes in peritoneal macrophage (M Phi) activation state and plasma contents of LPS, IL-8, PLA(2) and MDA were determined at 48 hours after escharectomy in the rats.. The cell viability and permeability of the HUVECs co-cultured with the serum from burn patients in E group was much better preserved than that in B group. On the other hand, the peritoneal M Phi activation and the plasma contents of LPS, IL-8, PLA(2) and MDA in C group were obviously decreased compared with those in D group.. Early postburn escharectomy to remove denatured burned tissue were proved to be helpful in ameliorating endothelial injury and in inhibiting activation of inflammatory cells. Therefore, early escharectomy was assumed to be beneficial in the prevention of postburn SIRS and MODS.

Topics: Adult; Animals; Burns; Cell Division; Cell Line; Cell Membrane Permeability; Culture Media, Conditioned; Dinoprostone; Endothelium, Vascular; Female; Humans; Interleukin-8; Lipopolysaccharides; Macrophages, Peritoneal; Male; Malondialdehyde; Multiple Organ Failure; Nitric Oxide; Phospholipases A; Random Allocation; Rats; Rats, Wistar; Time Factors; Tumor Necrosis Factor-alpha

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood-Brain Barrier; Brain Injuries; Female; Glasgow Coma Scale; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Regression Analysis; Survival Rate; Time Factors; Treatment Outcome

High density lipoproteins (HDLs) inhibit the cytokine-induced expression of endothelial cell adhesion molecules both in vitro and in vivo. We examined the ability of HDLs to mediate a functional anti-inflammatory effect by measuring their ability to prevent neutrophil adhesion and transmigration in vitro. Treatment of human endothelial cell cultures with physiologic concentrations of HDLs inhibited neutrophil binding by 68 +/- 5.9% (mean and se, n=6, P<0.05) and neutrophil transmigration by 48.7 +/- 6.7% (n=8, P<0.05). We then examined the effect of HDLs on inflammatory infiltration and subsequent multiple organ dysfunction syndrome (MODS), associated with trauma in a rat model of hemorrhagic shock. Rats given human HDLs (80 mg apo A-I/kg, i.v.) 90 min after hemorrhage (which reduced mean arterial pressure to 50 mmHg) and 1 min before resuscitation showed attenuation of the increases in the serum levels of markers of MODS normally observed in this model. Severe disruption of the architecture of tissues and the extensive cellular infiltration into those tissues were also largely inhibited in animals that received HDLs. Human HDLs attenuate the MODS associated with ischemia and reperfusion injury after hemorrhagic shock in rats.

Topics: Adult; Animals; Biomarkers; Cell Adhesion; Cell Movement; Cells, Cultured; Chemokine CXCL2; Chemokines; Disease Models, Animal; Endothelium, Vascular; Hemodynamics; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Kidney; Lipoproteins, HDL; Liver; Lung; Multiple Organ Failure; Muscles; Neurons; Neutrophils; P-Selectin; Pancreas; Recombinant Proteins; RNA, Messenger; Shock, Hemorrhagic

Priming of the polymorphonuclear neutrophil (PMN) response has been implicated in the activation of oxidative burst and tissue injury in patients with septic shock and acute renal failure (ARF). This study evaluated whether hemofiltration (HF) removes substances able to enhance the oxidative burst of PMNs.. Chemiluminescence (CL) priming activity induced by sera and ultrafiltrates of seven patients with septic shock, multiorgan dysfunction syndrome, and ARF (ARF/HF group) and of 10 uremic stable patients (Control/HF group) was evaluated on normal human PMNs stimulated with bacterial formyl-methionyl-leucyl-phenylalanine (FMLP). Patients submitted to HF were studied by determining blood and ultrafiltrate interleukin-8 (IL-8), platelet-activating factor (PAF), and CL priming activity at the beginning (T0), and after four hours (T4) of treatment.. Preincubation of normal human PMNs with sera and ultrafiltrates from septic patients induced a potent priming of CL activity in subsequent FMLP stimulation. In the ARF/HF group, the prefilter blood concentrations of IL-8 and CL PMN-priming activity significantly decreased during the four hours of HF treatment, with a loss of IL-8 in the ultrafiltrate of 6930 (median, range 4292 to 9282) ng per four hours. PAF detected in the ultrafiltrate and associated with the membrane (7.3 ng, range 1.45 to 9.89) was minimal. In the ARF/HF group, a significantly positive correlation between CL PMN-priming activity and IL-8 concentrations was observed. The CL priming activity in blood and ultrafiltrates was reduced to 55 and 46% by preabsorption with monoclonal antibody (mAb) anti-IL-8. In contrast, the PAF receptor antagonist WEB 2170 did not affect CL priming activity. In the control/HF group, the CL PMN-priming activity was significantly lower than in the ARF/HF group and was independent of IL-8.. Sera from septic patients demonstrate an enhanced CL priming activity on PMNs. This activity is reduced by ultrafiltration and is due, at least in part, to ultrafiltered IL-8.

Topics: Acute Kidney Injury; Aged; Blood Physiological Phenomena; Hemofiltration; Humans; Interleukin-8; Luminescent Measurements; Middle Aged; Multiple Organ Failure; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activating Factor; Reference Values; Respiratory Burst; Shock, Septic; Uremia

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Topics: Acute Kidney Injury; Acute-Phase Reaction; Animals; Anorexia; Ataxia; Bacteremia; Chronic Disease; Disease Progression; Escherichia coli Infections; Fever; Hematologic Diseases; Interleukin-6; Interleukin-8; Models, Animal; Multiple Organ Failure; Nephritis, Interstitial; Reproducibility of Results; Swine, Miniature; Systemic Inflammatory Response Syndrome

It is known that proinflammatory and anti-inflammatory cytokines are released during and after cardiopulmonary bypass (CPB) in infants and children. Sex steroids are known to have immunomodulatory functions, and release of the anti-inflammatory cytokine IL-10 is stimulated by progesterone in vitro. The purpose of the present study was to investigate the plasma levels of progesterone, IL-8 (proinflammatory cytokine) and IL-10, and to relate them to sex and postoperative morbidity.. Eighteen infants and children (eight female) undergoing CPB were prospectively studied. Plasma levels of progesterone, IL-8 and IL-10 were determined before and 10 min after the start of CPB, and immediately after CPB; and 6 h, 24 h, 3 days and 7 days postoperatively. Organ dysfunction was identified on the basis of arbitrarily defined criteria.. After CPB, all patients showed significant increases in plasma levels of progesterone, IL-8 and IL-10. Plasma levels of IL-10 were significantly higher in female patients, except for during the immediate postoperative period. According to the criteria used, six out of 10 male patients, but none of the female patients developed multiple organ dysfunction (MOD).. The present study shows that CPB induces a significant and marked increase in plasma levels of progesterone in infants and children. Studies of administration of progesterone-blocking substances to male and female animals may help to elucidate the roles of sex and progesterone in the setting of CBP.

Topics: Adolescent; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Humans; Infant; Interleukin-10; Interleukin-8; Intraoperative Period; Male; Multiple Organ Failure; Postoperative Complications; Progesterone; Prospective Studies; Sex Factors; Time Factors

To assess the ability of clinical or biochemical parameters to predict outcome (survival or non-survival; severe or moderate/no complication) using multiple regression analyses.. Prospective, descriptive cohort study with no interventions. 12 surgical intensive care units of university hospitals and large community hospitals; four medical school research laboratories in eight European countries. 128 surgical patients with major intra-abdominal surgery admitted for at least two days to an intensive care unit. Prediction of complications or survival based on analysis of clinical (Multiple Organ Dysfunction Score, Multi-Organ-Failure Score, Acute Physiology and Chronic Health Evaluation II scores) and immunological (plasma levels of endotoxin, endotoxin neutralizing capacity, IL-6, IL-8, cell associated IL-8, Fc-receptor polymorphism, soluble CD-14) parameters, with comparison of predicted and actual outcomes.. APACHE II, MODS score, MOF score, platelets, IL-6, IL-8, ENC, cell ass. IL-8 were significantly different between survivors and non-survivors and patients with/without severe complications by univariate analysis. By multivariate analysis only MOF, MODS score, IL-6, platelets, comorbidity predicted complications with a sensitivity of 82% and a specificity of 87%. Multivariate analysis demonstrated that only APACHE II score, plasma IL-8 and complications predicted death (sensitivity 84%; specificity 90%).. Immunological surrogate parameters may predict complications and death of surgical ICU patients. The use of several parameters may add to increase sensitivity and specificity in a prognostic model.

Topics: Anti-Bacterial Agents; APACHE; Cohort Studies; Endotoxins; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Models, Biological; Multiple Organ Failure; Multivariate Analysis; Outcome Assessment, Health Care; Prognosis; Prospective Studies; Receptors, Fc

The dynamic aspects of circulating cytokines and cytokine modulators and their relationship with development of multiple organ failure (MOF) in patients with acute pancreatitis were analyzed. All cytokine and C-reactive protein levels in the circulation were higher than those in the MOF group. In particular, plasma concentrations of soluble tumor necrosis factor receptors (sTNF-RI and sTNF-RII) were significantly higher in patients with MOF than in those without even at admission. Furthermore, plasma concentrations of sTNF-Rs and interleukin-1 (IL-1) receptor antagonist (IL-1ra) were much higher than those of their counterparts, TNFalpha and IL-beta, respectively. These results suggest that the plasma concentrations of sTNF-Rs are useful predictors for the development of MOF, and actions of TNF-alpha and IL-1beta could be regulated by their modulators (soluble receptor and receptor antagonist, respectively) in the pathologic condition of severe acute pancreatitis.

Topics: Acute Disease; Adolescent; Adult; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Tumor Necrosis Factor-alpha

The time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown.. In a prospective clinical study, we measured the proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and IL-8, the anti-inflammatory cytokine IL-10, interleukin 1 beta receptor antagonist (IL-1RA), and the soluble IL-2 receptor (sIL-2R), and correlated our findings with organ and systemic complications in acute pancreatitis. In 51 patients with acute pancreatitis admitted within 72 hours after the onset of symptoms, these parameters were measured daily for seven days. In addition, 33 aspirates from ascites and the lesser sac were measured.. Sixteen patients had mild acute pancreatitis (AP) and 35 severe AP (Atlanta classification); 18 patients developed systemic complications requiring treatment. All mediators were increased in AP. sIL-2R, IL-10, and IL-6 were significantly elevated in patients with distant organ failure. An imbalance in IL-1 beta/IL-1RA was found in severe AP and pulmonary failure. Peak serum sIL-2R predicted lethal outcome and IL-1RA was an early marker of severity. IL-6 was the best prognostic parameter for pulmonary failure.. Our results suggest that local mediator release, with a probable IL-1 beta-IL-1RA imbalance in severe cases, is followed by the systemic appearance of pro- and anti-inflammatory mediators. The pattern of local and systemic mediators in complicated AP suggests a role for systemic lymphocyte activation (triggered by local release of mediators) in distant organ complications in severe AP.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Inflammation Mediators; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Prognosis; Prospective Studies; Receptors, Interleukin-1; Receptors, Interleukin-2; Severity of Illness Index

Postinjury neutrophil (PMN) priming identifies the injured patient at risk for the subsequent development of multiple organ failure (MOF). PMN priming has previously been shown to cause enhanced release of proteases and superoxide. PMNs, however, are a rich source of proinflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor (TNF), which have been implicated in the development of MOF. PMNs also make IL-1ra, which is an anti-inflammatory cytokine that inhibits IL-1. It is our hypothesis that postinjury PMNs are primed for increased stimulated release of the proinflammatory cytokines IL-8 and TNF but not the anti-inflammatory cytokine IL-1ra.. Twelve trauma patients with a mean Injury Severity Score of 24 (+/-4.6) and 10 elective surgical patients were studied. Postinjury PMNs were isolated from blood obtained at presentation (within 2 hours after injury) and 24 hours after trauma. PMNs from elective surgical patients were obtained preoperatively, immediately postoperatively, and at 24 hours. The PMNs were stimulated with platelet-activating factor (200 nM)/N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L) or lipopolysaccharide (100 ng/mL) incubated for 24 hours in RPMI-1640, and release of IL-8, TNF, and IL-1ra were measured.. Postinjury PMNs were primed for both platelet-activating factor/N-formyl-methionyl-leucyl-phenylalanine-stimulated and lipopolysaccharide-stimulated IL-8 and TNF release at 2 hours after injury (fourfold increase of IL-8 release and fivefold increase of TNF release), whereas elective surgical patients demonstrated no priming. In contrast, postinjury patients were not primed for increased release of the counterinflammatory cytokine IL-1ra, suggesting a specific postinjury up-regulation of IL-8 and TNF.. After injury, PMNs are primed for proinflammatory cytokine release in addition to superoxide and elastase. This augmented release of IL-8 and TNF may be involved in the subsequent development of organ dysfunction and ultimately MOF.

Topics: Adult; Case-Control Studies; Cytokines; Female; Humans; Injury Severity Score; Interleukin-1; Interleukin-8; Male; Multiple Organ Failure; Neutrophils; Tumor Necrosis Factor-alpha; Wounds and Injuries

In this study the authors assessed the sequential release of lipid mediators (TXB2, PGE2, 6-keto-PGF1alpha, LTB4, LTC4, PAF), pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-10) in 17 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Time course of appearance of inflammatory mediators revealed the early and transient increase in lipid mediator plasma concentrations (6-keto-PGF1alpha, LTB4, LTC4, PAF) whereas cytokines (IL-6, IL-8, IL-10) were involved only in late pre- and post-operative periods. No variation of TXB2, PGE2, IL-4 and TNF-alpha levels were found. No correlation was documented between the levels of lipid mediators and pro- or anti-inflammatory cytokines suggesting that lipidic compounds are not implicated in the genesis of cytokines which appear much later involved. Despite the common use of high doses of aprotinin (a non-specific enzyme inhibitor) in hope to abrogate the inflammatory response to cardiopulmonary bypass procedure, this study reports the persistent release of several inflammatory compounds that might be involved in the post-CABG multiple organ failure syndromes.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents; Cardiopulmonary Bypass; Cytokines; Dinoprostone; Extracorporeal Circulation; Humans; Inflammation Mediators; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Leukotriene B4; Leukotriene C4; Lipid Metabolism; Lipids; Multiple Organ Failure; Platelet Activating Factor; Prospective Studies; Thromboxane B2; Tumor Necrosis Factor-alpha

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.

Topics: Adrenomedullin; Adult; Aged; APACHE; Critical Care; Female; Humans; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Peptides; Prognosis; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Vasodilator Agents

To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2-5, and that in NOF patients was 0-1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; APACHE; Biomarkers; Blood Cell Count; C-Reactive Protein; Community-Acquired Infections; E-Selectin; Female; Humans; Interleukin-6; Interleukin-8; Macrophage-1 Antigen; Male; Middle Aged; Multiple Organ Failure; Receptors, Interleukin-2; Shock, Septic

To test the hypothesis that elevated interleukin (IL)-10 plasma concentration relative to IL-6 and IL-8 in patients with acute pancreatitis is associated with improved clinical outcome.. Case series.. University hospital surgical and intensive care unit.. Patients with mild (n = 18) and severe (n = 14) acute pancreatitis were recruited within 12 hrs of admission and studied for 5 days.. None.. The plasma concentration of IL-10 was significantly elevated in patients with severe pancreatitis during the 5 days and especially so in those who died compared with survivors on day 5 (p <.03). The ratio of IL-10/IL-6 was decreased in patients with severe pancreatitis on day 5 (p < .01). There was a significant decrease in the ratio of IL-10/IL-8, but not of IL-10/IL-6, during the first 5 days (p < .014).. The findings are consistent with the hypothesis that an increase in plasma IL-10 relative to IL-6 or IL-8 is associated with improved clinical outcome.

Topics: Acute Disease; Adult; Aged; Female; Humans; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome

To further improve the treatment of burn wound sepsis.. Eight patients with burn wound sepsis, of whom 6 with MODS and two with septic shock, were treated consecutively in our hospital from September 1997 to October 1998. The plasma concentrations of IL-6, IL-8 TNF and LPS were assayed before and after surgical intervention and at the time when the patients' vital signs became stable.. (1) The patients' conditions abruptly deteriorated when the burn wound sepsis emerged. (2) The major causative factor related to burn wound sepsis was extensive burn injuries, with large area of deep burn remained open. (3) Although colonization by multiple pathogenic bacteria was found, Pseudomonas aeruginosa was the most frequent bacteria isolated from the subeschar tissue. (4) The plasma concentrations of IL-6, IL-8, TNF and LPS before surgical intervention were significantly higher than those after surgical intervention (P < 0.05); (5) The lowest level of the inflammatory mediators were observed when the conditions of patients became stable, and the values were significantly lower compared with those before surgical intervention (P < 0.001).. The main cause of burn wound sepsis is the presence of a large area of infected open deep burn wounds, which should be excised and covered early. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn wound sepsis. Favorable results in the treatment attribute to appropriate application of multiple treatments, and early, aggressive and thorough surgical excision of invasive burn infectious tissue and closure of wounds play a crucial role.

Topics: Adolescent; Adult; Burns; Child; Female; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Multiple Organ Failure; Shock, Septic; Wound Infection

The excessive uncontrolled activation of inflammatory cells and mediators after trauma or major surgery plays a key role in the development of adult respiratory distress syndrome and multiple organ system failure (MOSF). In the past elevated cytokine levels were shown to influence the outcome of these patients adversely. There are diverging results regarding the removal of circulating cytokines by various methods of hemopurification for clinical improvement of MOSF. Seven patients after trauma or major surgery underwent continuous venovenous hemofiltration (CVVH) for the treatment of severe organ failure of the heart and lungs (Murray score 2.74) but not for renal or liver failure. The cytokine levels were measured at the beginning and 15, 60, 120, and 240 minutes after initiation of CVVH (measure points MP1-5). Clinical improvement during the treatment was monitored, and correlation with cytokine levels was evaluated. Arterially measured tumor necrosis factor alpha rose from 11.14 ng/ml to 17.86 ng/m1 (p < 0.05). Arterial interleukin-6 (IL-6) levels significantly decreased during CVVH from 1284.7 ng/m1 to 557.9 ng/m1; IL-8 levels simultaneously decreased from an initial peak of up to 154.4 ng/m1 at MP3 to 97.3 ng/m1 at MP5. The drop in serum IL-6 and IL-8 levels closely correlated with clinical improvement. After 2 hours of CVVH the hemodynamic situation improved significantly, as revealed by a decrease in catecholamine expenditure, an increase in arterial pressure, and a decrease in pulmonary artery pressure. Moreover, 2 hours after the initiation of CVVH the oxygenation index rose significantly and correlated well with the drop in shunt fraction. The Murray score significantly fell to 1.86. The removal of IL-6 and IL-8 by CVVH after initial stimulation correlates with clinical improvement, which was demonstrated by significantly improved oxygenation and hemodynamics from 2 hours after the initiation of CVVH onward. The elimination of cytokines and several mediators by CVVH may contribute to the cardiopulmonary improvement of critically ill patients. In comparison with the clinical control group (n = 7), which was comparable in terms of MOSF, no intervention led to a similar improvement in cardiorespiratory failure, and overall two of these patients died. Moreover, patients of the control group experienced a significant longer stay at in the intensive care unit.

Topics: Adult; Cytokines; Female; Hemodynamics; Hemofiltration; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Tumor Necrosis Factor-alpha

The objective of this study was to determine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in septic patients with neutropenia.. Twenty consecutive septic patients were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days (group G). They were compared with 14 septic patients treated earlier without rhG-CSF (group N). All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL. Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's Multiple Organ Failure (MOF) index were evaluated. In addition, nucleated cell count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an indicator of the tissue injury were evaluated in group G.. In group G, TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL-6, and IL-8 decreased reciprocally. There was no deterioration of LE and RI. Consequently, the APACHE II score and MOF index improved. In group N, however, CRP showed no change concomitant with the APACHE II score and MOF index.. Administration of rhG-CSF attenuates inflammatory responses without inducing tissue injury in septic patients with neutropenia.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; APACHE; Biomarkers; C-Reactive Protein; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Lenograstim; Leukocyte Count; Leukocyte Elastase; Male; Middle Aged; Multiple Organ Failure; Neutropenia; Recombinant Proteins; Sepsis; Tumor Necrosis Factor-alpha

This study investigated whether cytokines and colony-stimulating factors can predict prognosis in patients with postoperative multiple organ failure (MOF). We evaluated 14 patients with postoperative MOF who underwent operation for cardiovascular disease. Seven patients recovered from MOF (survivors) and seven did not recover and died (nonsurvivors). The white blood cell (WBC) count, granulocyte colony-stimulating factor, monocytic colony-stimulating factor, interleukin-6 (IL-6), and IL-8 were measured on the day the patients were judged to be in MOF and each week thereafter until the patients recovered or died. Survivors and nonsurvivors were equivalent in terms of age, gender, proportion of use of extracorporeal circulation, operation time, volume of blood transfusion, time from operation to the onset of MOF, the MOF score, proportion of bacteremia, duration of MOF, and number of failed organs. The mean duration of MOF was less than 2 weeks in both groups; therefore the measurements were compared on the first day of MOF and 1 week later. No significant differences between the two groups in terms of WBC counts, colony-stimulating factors, and IL-6 levels were noted. However, the serum level of IL-8 was significantly higher in nonsurvivors than in survivors. Patients with a high serum levels of IL-8 at the time of MOF had a poor prognosis.

Topics: Aged; Aged, 80 and over; Bacteremia; Blood Transfusion; Cause of Death; Extracorporeal Circulation; Female; Follow-Up Studies; Forecasting; Granulocyte Colony-Stimulating Factor; Heart Diseases; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Macrophage Colony-Stimulating Factor; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Prognosis; Survival Rate; Time Factors

Most prognostic indices for severely injured patients are based on anatomical findings and the vital signs. The posttraumatic organ failure, however, is thought to be triggered by the initial inflammatory response. The objective of this study was to evaluate the correlation between the early activation of inflammation and the rate of organ failure and death.. Sixty-six patients with multiple injuries (Injury Severity Score > 18, age 18-70 years, admission within 6 hours after accident, survival > 48 hours) were included in this prospective study. During a 14-day observation period, serial blood samples were collected starting within 30 minutes after admission. Plasma levels of neutrophil elastase, lactate, antithrombin III, and interleukin-6 and -8 were determined. The clinical course and the degree of organ failure were recorded daily until death or transfer to a general ward.. The 66 severely injured patients had a mean Injury Severity Score of 40 points. Eleven patients died from multiple organ failure (group 1), 38 subjects survived a single or multiple organ failure (group 2), and 17 patients had an uneventful recovery (group 3). The initial plasma concentrations for neutrophil elastase (650 vs. 355 ng/mL), lactate (5.0 vs. 3.1 mmol/L), antithrombin III (48 vs. 62% from normal), interleukin-6 (703 vs. 177 pg/mL), and interleukin-8 (1,101 vs. 301 pg/mL) were significantly different between groups 2 and 3 already in the initial posttraumatic period. Patients from group 1 presented with significantly higher levels of these parameters as early as 24 hours after trauma compared with group 2. Different patterns were identified with respect to early versus late posttraumatic organ failure.. These data show that the degree of the initial inflammatory response corresponds with the development of posttraumatic organ failure. Besides anatomically and physiologically based trauma scores, these parameters might be used as indicators for the injury severity.

Topics: Adolescent; Adult; Aged; Antithrombin III; Humans; Injury Severity Score; Interleukin-6; Interleukin-8; Lactates; Leukocyte Elastase; Middle Aged; Multiple Organ Failure; Multiple Trauma; Prognosis; Prospective Studies; Systemic Inflammatory Response Syndrome; Time Factors

Systemic inflammatory response syndrome (SIRS) and infections are frequently associated with the development and progression of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). We investigated, at onset and during the progression of ARDS, the relationships among (1) clinical variables and biological markers of SIRS, (2) infections defined by strict criteria, and (3) patient outcome. Biological markers of SIRS included serial measurements of inflammatory cytokines (IC)-tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL) 1 beta, 2, 4, 6, and 8-in plasma and BAL fluid.. We prospectively studied two groups of ARDS patients: 34 patients treated conventionally (group 1) and nine patients who received glucocorticoid rescue treatment for unresolving ARDS (group 2). Individual SIRS criteria and SIRS composite score were recorded daily for all patients. Plasma IC levels were measured by enzyme-linked immunosorbent assay on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients received mechanical ventilation. Unless contraindicated, bilateral BAL was performed on day 1, weekly, and when ventilator-associated pneumonia was suspected. Patients were closely monitored for the development of nosocomial infections (NIs).. ICU mortality was similar among patients with and without sepsis on admission (54% vs 40%; p < 0.45). Among patients with sepsis-induced ARDS, mortality was higher in those who subsequently developed NIs (71% vs 18%; p < 0.05). At the onset of ARDS, plasma TNF-alpha, IL-1 beta, IL-6, and IL-8 levels were significantly higher (p < 0.0001) in nonsurvivors (NS) and in those with sepsis (p < 0.0001). The NS group, contrary to survivors (S), had persistently elevated plasma IC levels over time. In 17 patients, 36 definitive NIs (17 in group 1 and 19 in group 2) were diagnosed by strict criteria. No definitive or presumed NIs caused an increase in plasma IC levels above patients' preinfection baseline. Daily SIRS components and SIRS composite scores were similar among S and NS and among patients with and without sepsis-induced ARDS, were unaffected by the development of NI, and did not correlate with plasma IC levels.. Sepsis as a precipitating cause of ARDS was associated with higher plasma IC levels. However, NIs were not associated with an increase in SIRS composite scores, individual SIRS criteria, or plasma IC levels above patients' preinfection baseline. SIRS composite scores over time were similar in S and NS. SIRS criteria, including fever, were found to be nonspecific for NI. Irrespective of etiology of ARDS, plasma IC levels, but not clinical criteria, correlated with patient outcome. These findings suggest that final outcome in patients with ARDS is related to the magnitude and duration of the host inflammatory response and is independent of the precipitating cause of ARDS or the development of intercurrent NIs.

Topics: Adult; Bacterial Infections; Biomarkers; Bronchoalveolar Lavage Fluid; Cause of Death; Critical Care; Cross Infection; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glucocorticoids; Humans; Interleukin-1; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Male; Multiple Organ Failure; Outcome Assessment, Health Care; Pneumonia; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome; Survival Rate; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Cardiopulmonary bypass constitutes an injury that may cause postoperative pathophysiological changes due to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). These complications include coagulopathy, hypotension, capillary leakage, and multiple organ injury. To investigate the role of endotoxin and cytokines in the response to bypass injury, we measured plasma levels of endotoxin and proinflammatory cytokines in 20 pediatric patients before and after bypass. Clinical data, including duration of injury and tests indicative of SIRS/MODS, were collected. Levels of endotoxin, TNF-alpha, IL-6, and IL-8 but not IL-1 beta were significantly increased after bypass. Most of the cytokines have been found to correlate with each other. Endotoxin did not correlate with duration of bypass, cytokines, or SIRS/MODS. In contrast, TNF-alpha and IL-8 correlated with duration of bypass and were associated with SIRS/MODS. Certain clinical complications were associated with specific cytokines. Understanding the role of cytokinemia in SIRS/MODS may lead to better prognostic assessment and therapeutic modalities.

Topics: Cardiopulmonary Bypass; Child, Preschool; Cytokines; Endotoxins; Female; Humans; Inflammation; Interleukin-1; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Multiple Organ Failure; Prognosis; Time Factors; Tumor Necrosis Factor-alpha

In 17 patients plasma TNF-alpha and IL-8 were assayed with enzyme-linked immunosorbent assay. IL-6 activity in plasma was determined by bioassay with IL-6-dependent cell line 7TD1. The limulus amoebocyte lysate chromogenic test was used for plasma endotoxin assay. Plasma cytokine levels in injured patients were significantly increased. Plasma TNF-alpha was shown to be increased earlier, while an increase in plasma IL-6 and IL-8 levels occurred late, all of which were shown to be significantly positively correlated with ISS, cardiac and hepatic enzyme activities, and index of renal function. In addition, obvious endotoxaemia occurred at an early stage of injuries, which was respectively significantly correlated with ISS and plasma TNF-alpha, IL-6 and IL-8 levels. Severe injuries could induce increased successive release of TNF-alpha, IL-6 and IL-8, and obvious endotoxaemia. The post injury release of cytokines might be related to endotoxaemia, and may play an important role in the development of organ damage after injury.

Topics: Adolescent; Adult; Aged; Cytokines; Endotoxemia; Endotoxins; Enzymes; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Tumor Necrosis Factor-alpha; Wounds and Injuries

We investigated kinetics of plasma TNF, IL-6 and IL-8 and their relationship with organ dysfunction and endotoxemia in 17 patients with severe trauma in order to further elucidate the role of cytokines in the development of organ damage and their production mechanism after trauma. Plasma cytokine levels significantly increased in trauma patients, and their plasma TNF was increased earlier. The cytokines were positively correlated with ISS, cardiac and hepatic enzyme activities, index of renal function, and plasma endotoxin levels. It is suggested that TNF, IL-6 and IL-8 may participate in the development of organ damage after trauma, and its release might be related to massive endotoxin translocation into body at the early stage of trauma.

Topics: Adolescent; Adult; Aged; Endotoxins; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Tumor Necrosis Factor-alpha; Wounds and Injuries

Topics: Hemofiltration; Humans; Interleukin-6; Interleukin-8; Middle Aged; Multiple Organ Failure; Systemic Inflammatory Response Syndrome

Interleukin-6 (IL-6), interleukin-8 (IL-8), and adhesion molecules have been implicated as mediators in neutrophil (PMN) and endothelial cell (EC) interactions leading to postinjury multiple organ failure (MOF). Our hypothesis was that circulating levels of IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) would discriminate patients at risk for postinjury MOF.. Serial plasma levels of IL-6, IL-8, and sICAM-1 were measured in 27 high-risk trauma patients.. The IL-6 and IL-8 levels were significantly elevated in MOF patients compared with non-MOF patients at 12 and 36 hours postinjury. The IL-6 level was also elevated at 84 and 132 hours, and IL-8 at 84 hours. The sICAM-1 level did not become elevated in MOF patients until 132 hours postinjury.. Interleukin-6 and IL-8 are elevated early after trauma and discriminate patients who will develop MOF. Late elevation of sICAM-1 likely results from PMN cytotoxicity leading to EC injury or inflammation.

Topics: Adult; Awards and Prizes; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Multiple Organ Failure; Prospective Studies; Risk Factors; Wounds and Injuries

Plasma from 33 patients at risk of multiple organ failure (MOF) after major trauma was tested for a priming effect on neutrophils, and for the presence of platelet-activating factor (PAF) activity and interleukin (IL) 8. Plasma sampled at 3, 6, 12 and 24 h after injury significantly primed normal neutrophils to release mean(s.e.m.) 1.26(0.19), 1.33(0.26), 1.04(0.14) and 0.86(0.13) nmol superoxide per min per 1.3 x 10(6) neutrophils respectively (P < 0.05). Priming at 3 h after injury was inhibited by mean(s.e.m.) 63.8(7.0) per cent by the PAF antagonist, WEB 2170 (P < 0.01). Mean(s.e.m.) plasma IL-8 was raised at 6 and 12 h after injury to 785(183) and 836(175) pg/ml (P < 0.01). At 12 h after injury the plasma IL-8 level correlated directly with the number of units of red blood cells transfused (r = 0.64, P < 0.01), and was significantly higher in the group of six patients who developed MOF (P < 0.05). These data suggest that after trauma the mediators PAF and IL-8 appear sequentially in the circulation, are potential mechanisms of circulating neutrophil priming, and that IL-8 may also be an early biochemical marker predicting the onset of MOF.

Topics: Adolescent; Adult; Aged; Female; Humans; Injury Severity Score; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Neutrophils; Platelet Activating Factor; Time Factors; Wounds and Injuries

We studied blood MIP-1 alpha and IL-8 in 38 septic patients and 5 healthy volunteers. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 alpha was detected in 45% of the patients and Il-8 in 84%. The levels of MIP-1 alpha, but not of IL-8, correlated with CRP, IL-6 and TNF alpha levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 alpha levels. In contrast, we found increased levels of serum IL-8 in septic patients with disseminated intravascular coagulation, central nervous system (CNS) dysfunction or renal failure, and the mortality rate was higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05). In conclusion, the production of both MIP-1 alpha and IL-8 was increased and initially detectable levels of circulating IL-8 predicted high mortality in sepsis.. To determine the significance of the C-C chemokine MIP-1 alpha and the C-X-C chemokine IL-8 in sepsis.. Prospective study.. Clinical investigation, emergency department and general intensive care unit of university hospital.. 38 septic patients and 5 healthy volunteers were studied. Sepsis was diagnosed following the criteria formulated by ACCP/SCCM.. 10-20 ml of blood was drawn from each patient at the time of initial diagnosis of sepsis.. MIP-1 alpha and IL-8 were determined by sandwich ELISA. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 alpha was detected in 45% of the patients and IL-8 was detected in 84%. The levels of MIP-1 alpha, but not of IL-8, correlated with CRP, IL-6 and TNF alpha levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 alpha levels. In contrast, we found increased levels of serum IL-8 in patients with disseminated intravascular coagulation (DIC) (p < 0.05), central nervous system (CNS) dysfunction (p < 0.05), renal failure (p < 0.01) and the mortality rates were higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05).. The production of MIP-1 alpha and IL-8 was increased in sepsis. Furthermore, an initially detectable level of circulating IL-8, but not MIP-1 alpha, predicted a high mortality in sepsis diagnosed according to the ACCP/SCCM criteria.

Topics: Biomarkers; Case-Control Studies; Chemokine CCL4; Disseminated Intravascular Coagulation; Female; Humans; Interleukin-8; Japan; Macrophage Inflammatory Proteins; Male; Middle Aged; Multiple Organ Failure; Prognosis; Prospective Studies; Sepsis; Statistics, Nonparametric

To determine whether continuous venovenous hemodialfiltration (CVVHD) is associated with the extraction of interleukin-6 (IL-6) and interleukin-8 (IL-8) from the circulation of critically ill patients with septic acute renal failure. To quantitate their clearance and assess any possible effect of CVVHD on these cytokines' serum concentrations.. Prospective controlled study of IL-6 and IL-8 removal by CVVHD in patients with septic acute renal failure.. Intensive care unit of a tertiary institution.. Ten critically ill patients with sepsis, acute renal failure, and multiorgan failure. A control group of five patients experiencing an acute illness while undergoing chronic hemodialysis.. Collection of blood samples before CVVHD. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 h of treatment. IL-8 concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extractions were calculated.. IL-6 and IL-8 were detected in the blood of all patients with septic acute renal failure prior to CVVHD. The median IL-6 blood level was 103 pg/mL (range: 19 to 900) and the median IL-8 blood level was 200 (range: 32 to 2925). Both cytokines were cleared by the hemofilter during CVVHD. The median hemofilter clearance of IL-6 were 1.99 L/day (range: 0 to 8.5) and the median clearance of IL-8 was 3.95 L/day (range: 0.31 to 42.8). These blood levels and clearances resulted in median daily extraction rates of 194 ng of IL-6 (range: 0 to 9031) and of 915 ng of IL-8 (range 47.5 to 3562). Control patients had negligible amounts of either IL-6 or IL-8 in their ultrafiltrate. The rate of extraction for IL-6 correlated with its blood levels (p < 0.0001). This was not true for IL-8. A correlation between IL-6 levels and the patients' white cell counts was found after 24 h of hemofiltration.. CVVHD is associated with the extraction of IL-6 and IL-8 from the circulation of patients with septic multiorgan and renal failure. The biological significance of such extraction is undetermined, but such cytokine removal highlights the complexity of the effect of continuous hemofiltration on the soluble mediators of inflammation activated during human sepsis.

Topics: Acute Kidney Injury; APACHE; Case-Control Studies; Female; Hemodiafiltration; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Sepsis

Serum levels of interleukin-6, interleukin-8, the soluble receptor for tumor necrosis factor (sTNFr), and the soluble receptor for intercellular adhesion molecule-1 (sICAM-1) were measured serially in a series of 13 severely injured trauma patients to determine if any of these elements of the inflammatory response are predictive of multiple organ failure (MOF). Six of the 13 patients developed MOF as determined by a MOF scoring system. At the completion of resuscitation (when oxygen delivery and consumption were maximized) sICAM-1 levels were significantly higher in MOF patients before the development of clinical evidence of organ failure (700 +/- 67 ng/mL) compared with non-MOF patients (302 +/- 18 ng/mL). There was a significant correlation between the absolute level of sICAM-1 at the time of resuscitation and the severity of subsequent MOF. This finding suggests that leukocyte-endothelial cell interactions are upregulated immediately after injury and may be implicated in the end-organ injury that leads to MOF.

Topics: Adult; Aged; Cell Adhesion Molecules; Cytokines; Female; Humans; Injury Severity Score; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Tumor Necrosis Factor-alpha

Topics: Animals; Cytokines; Humans; Interleukin-8; Multiple Organ Failure; Shock, Septic

Interleukin (IL)-8, a pro-inflammatory cytokine, is a potent chemoattractant factor and an activator of neutrophils produced by many cell types after stimulation by IL-1, tumor necrosis factor (TNF), or microbial products such as endotoxins. We investigated whether the presence of measurable IL-8 in plasma was associated with the clinical status of severely ill septic or nonseptic patients susceptible to the development of multiple organ failure.. Cohort study.. A collaborative study between an intensive care unit and a research laboratory.. Circulating IL-8 concentrations were measured in the plasma of 27 patients with sepsis syndrome and in 16 patients with noninfectious shock because these two conditions put patients at risk for the development of multiple organ failure. Sixteen of 27 patients with severe infection and 13 of 16 patients with noninfectious pathologies developed multiple organ failure.. A specific enzyme-linked immunosorbent assay (ELISA) for IL-8 was set up with a monoclonal and a rabbit polyclonal antihuman IL-8 using a sandwich technique. High concentrations of circulating IL-8 were found in the plasma of patients with sepsis syndrome. Among septic patients, a significant difference was observed between concentrations of IL-8 in survivors (n = 16) and nonsurvivors (n = 11) (81 +/- 13 pg/mL vs. 3326 +/- 1219 pg/mL, respectively; p = .001). A correlation was noticed between plasma IL-8 and IL-6 concentrations (r2 = .42; p = .001), while no correlation was observed between IL-8 and TNF-alpha values, or between IL-8 and IL-1 beta. Although the mortality rate of nonseptic, multiple organ failure patients was 92%, low plasma concentrations of IL-8 were found (78 +/- 34 pg/mL), while high plasma concentrations were measured in septic, multiple organ failure patients (mortality rate 69%) who were sampled at a similar stage. By contrast, increased IL-6 values were observed in both septic and nonseptic, multiple organ failure patients.. In septic patients, high amounts of circulating IL-8 concentrations correlate with fatal outcome, whereas only low plasma concentrations of IL-8 are present in patients with nonseptic, multiple organ failure. This finding suggests that the signals involved in the exacerbation of IL-8 production are different, depending on infectious or noninfectious etiology.

Topics: Aged; Bacterial Infections; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Middle Aged; Multiple Organ Failure; Prognosis; Shock

Topics: Adhesiveness; Age Factors; Animals; Antibodies, Monoclonal; Antigens, CD; CD11 Antigens; CD18 Antigens; Cell Adhesion Molecules; Cell Movement; Disease Models, Animal; Endothelium; Humans; Infant, Newborn; Inflammation; Interleukin-8; Multiple Organ Failure; Neutrophils; Platelet Activating Factor; Receptors, Leukocyte-Adhesion; Reperfusion Injury; Respiratory Distress Syndrome

To determine the effects of accidental injury of varying severity on interleukin (IL)-1 alpha, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and endotoxin release.. Prospective, multi-unit, longitudinal study.. Emergency Departments and intensive care units of two university hospitals.. Trauma patients after mild, moderate, and severe injury (Injury Severity Score of < or = 10, 11 to 24, and > or = 25, respectively).. None.. Plasma cytokine and endotoxin concentrations were measured over a 5-day period, starting within 2 hrs of accidental injury. An enzyme-linked immunosorbent assay was used to determine plasma concentrations of IL-1 alpha, IL-6, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured using a chromogenic limulus amebocyte assay. Preresuscitation samples obtained immediately on arrival in the Emergency Department, and within 2 hrs of injury, demonstrated significant increases of IL-6 and IL-8 concentrations in the severe injury group, in contrast to minimal increases seen after mild or moderate injury. Analysis of serial postresuscitation samples demonstrated rapid increases in IL-6 and IL-8 concentrations within 12 hrs of injury. IL-6 and IL-8 remained increased for 24 hrs after injury, then decreased markedly from their peak values during the next 24 hrs. Increased circulating concentrations of these cytokines continued to be present for > 5 days in the severely injured patients. IL-6 and IL-8 concentrations were only minimally increased in patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1 alpha were not found in any samples, including those samples obtained serially from severely injured patients. No patient at any time point had TNF-alpha concentrations of > 35 pg/mL.. These results demonstrate that severe injury produces rapid, large increases in circulating concentrations of IL-6 and IL-8 that may contribute to the frequent development of the adult respiratory distress syndrome and multiple organ system failure in this clinical setting.

Topics: Adult; Endotoxins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Injury Severity Score; Interleukin-1; Interleukin-6; Interleukin-8; Limulus Test; Longitudinal Studies; Male; Multiple Organ Failure; Multiple Trauma; Prospective Studies; Respiratory Distress Syndrome; Resuscitation; Time Factors; Tumor Necrosis Factor-alpha