interleukin-8 and Shock

Time relationships of physiologic patterns that are relevant to the pathogenesis of adult respiratory distress syndrome (ARDS) have not been well studied. The purpose of this review is to summarize the temporal relationship of blood volume, hemodynamics, and oxygen transport patterns occurring in postoperative patients before and after ARDS in order to develop a more complete mechanistic evaluation of its pathophysiology and to propose more rational therapeutic strategies. The data indicate that hypovolemia, reduced or uneven blood flow, inadequate delivery of oxygen, and insufficient consumption of oxygen precede the appearance of ARDS and are the primary precipitating physiologic events. This is contrary to conventional thinking which emphasizes capillary leak and fluid overload as the primary problems. The conventional approach also ignores events antecedent to ARDS that produce hypoxia of the lung tissue, result in pulmonary vasoconstriction, and increased pulmonary venous admixture (shunt). Therapy to prevent or rapidly treat these antecedent events has been shown to prevent or attenuate postoperative and posttraumatic ARDS. Various mediators such as interleukin (IL)-1, IL-6, and IL-8 and tumor necrosis factor as measured by plasma concentrations do not precede diagnostic criteria of ARDS, but may accelerate and augment the disorder as it is occurring.

Topics: Blood Volume; Capillary Permeability; Clinical Trials as Topic; Female; Fluid Therapy; Hemodynamics; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Oxygen Consumption; Postoperative Complications; Precipitating Factors; Prospective Studies; Pulmonary Edema; Respiratory Distress Syndrome; Shock; Survival Rate; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

To explore the effects of different methods of fluid resuscitation on the levels of inflammatory mediators during burn shock stage.. Twenty-four miniature swine were numbered from 1 to 24 and randomly divided by EXCEL 2007 into 4 groups of succinylated gelatin, hydroxyethyl starch, Parkland and allogeneic plasma (n = 6 each). Severe burn shock model was established. Succinylated gelatin, hydroxyethyl starch (130/0.4), Ringer's lactate and swine allogenic plasma were used as resuscitation fluid (alternative colloid) according to the burn shock recovery principles (beginning at 2 h post-injury). The parameters of heart rate (HR), blood pressure (BP), urine volume and central venous pressure (CVP) before and within 48 h post-burn were recorded. And the levels of tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β and IL-8 were measured at the time of pre-injury as well as 4 h, 8 h, 24 h and 48 h post-injury. Statistical analyses were performed.. All swine survived the shock stage. TNF-α in succinylated gelatin group was significantly higher at 48 h post-injury than that in allogeneic plasma group ((351 ± 74) vs (215 ± 44) ng/L, P < 0.05). TNF-α in hydroxyethyl starch group was significantly higher at 8 h post-injury than that in allogeneic plasma group ((327 ± 38) vs (249 ± 29) ng/L, P < 0.05). And they were both higher than the pre-burn levels (both P < 0.05). Compared with pre-injury ((508 ± 64) ng/L), the level of IL-1β in succinylated gelatin group increased substantially at 4 h ((563 ± 76) ng/L), 8 h ((589 ± 76) ng/L) and 48 h ((736 ± 42) ng/L) post-injury (all P < 0.05). The hydroxyethyl starch group was higher at 48 h post-injury than that at pre-injury ((574 ± 72) vs (492 ± 41) ng/L, P < 0.05). Also in Parkland group, the levels were higher at 24 h and 48 h hours post-injury than that at pre-injury ((575 ± 31), (584 ± 65) vs (498 ± 33) ng/L, both P < 0.05). Only succinylated gelatin group was significantly higher (P < 0.01) at 48 h post-injury than allogeneic plasma group ((561 ± 48) ng/L). Compared with pre-injury ((561 ± 48) ng/L), the level of IL-8 in succinylated gelatin group increased significantly at 8 h ((1012 ± 100) ng/L), 24 h post-burn ((993 ± 87) ng/L), significantly higher than allogeneic plasma group ((866 ± 99) ng/L) at 24 h (all P < 0.05). Although hydroxyethyl starch and Parkland groups increased significantly at 4 h post-injury and 8 h, 48 h post-injury versus those at pre-injury (all P < 0.05). There was no significant difference at each time point compared with pre-burn (P > 0.05).. The recovery regimens of hydroxyethyl starch and Parkland groups may restrain the levels of inflammatory mediators. And the effects are similar to those of allogeneic plasma group.

Topics: Animals; Burns; Disease Models, Animal; Female; Fluid Therapy; Inflammation; Interleukin-1beta; Interleukin-8; Resuscitation; Shock; Swine; Swine, Miniature; Tumor Necrosis Factor-alpha

Our objective was to evaluate the role of the liver for procalcitonin (PCT) and cytokine induction in a baboon endotoxin shock model. Complete liver resection with portocaval anastomosis was established in a baboon prior to the induction of endotoxin shock by intravenous administration of endotoxin (100 microg/kg LPS Escherichia coli). Two baboons without surgical intervention were used as controls. Plasma concentrations of PCT, tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, IL-8, endotoxin, and hemodynamic and metabolic parameters were measured pre- and postoperatively and until 6 h after endotoxin administration. PCT concentrations increased to 1.2 and 4.6 ng/mL in control animals at 6 h, but remained below 0.3 ng/mL in the anhepatic baboon. IL-6 and IL-8 increased only for few hours in controls, but remained elevated in the hepatectomized animal near their maximum (IL-6, 2-6 ng/mL) or several-fold higher (IL-8, 30-35 ng/mL), whereas TNF-alpha response was only a small fraction (0.3 ng/mL) of the controls. Endotoxin was much higher and longer persisting in the hepatectomized animal compared with controls. The near absence of PCT production in the anhepatic baboon suggests a primary role for the liver as a source of PCT production during endotoxin shock. Furthermore, the liver also seems to be an important source of TNF-alpha, but not IL-6 or IL-8.

Topics: Animals; Calcitonin; Cytokines; Endotoxins; Interleukin-6; Interleukin-8; Liver; Male; Papio; Protein Precursors; Shock; Time Factors; Tumor Necrosis Factor-alpha

In the process of developing a model of Escherichia coli endotoxin-induced acute lung injury and shock in specific pathogen-free pigs, the effects of pretreatment with metyrapone (a cortisol-synthesis inhibitor) were examined. Metyrapone was administered 1.5 h before start of endotoxin infusion at t = 0 h (MET-ETOX group, n = 6). At the end of the experiments (t = 4 h) a bronchoalveolar lavage (BAL) was performed. Control animals received only endotoxin (CON-ETOX group, n = 6) or metyrapone (MET-CON group, n = 4). The following results are presented as means +/- SEM. It was found that metyrapone successfully blocked endogenous cortisol synthesis (plasma cortisol levels were 41.0 +/- 5.9 nM in MET-ETOX vs. 339.0 +/- 37.7 nM in CON-ETOX at t = 4 h, P <0.01). At t = 4 h the MET-ETOX animals had substantially increased systemic hypotension compared to the CON-ETOX group (mean arterial pressure 26.7 +/- 4.3 vs. 77.7 +/- 12.2 mmHg, P <0.01), decreased dynamic lung compliance (10.9 +/- 0.7 vs. 13.7 +/- 0.6 ml/cmH2O, P <0.01), increased percentage of BAL neutrophils (28.4 +/- 6.5 vs. 6.6 +/-1.8, P <0.01), pulmonary edema (BAL total protein 0.82 +/- 0.21 vs. 0.42 +/- 0.09 mg/mL, P <0.05), elevated levels of interleukin-8 (1924 +/- 275 vs. 324 +/- 131 pg/mL, P <0.01) and acidosis (pH 7.11 +/- 0.03 vs. 7.23 +/- 0.06, P <0.05). The MET-ETOX group also showed an increased pulmonary hypertension between 2 and 3 h after start of endotoxin infusion and a trend toward significantly increased levels of plasma interleukin-8 (P = 0.052). Arterial pCO2, pO2/FiO2, plasma endothelin-1, plasma TNFalpha, and blood leukocytes were not markedly influenced by the plasma cortisol levels. Nitric oxide production did not seem to be altered by endotoxin infusion in this model, in contrast to other animal studies; this discrepancy could be thought to be due to endotoxin-dosage differences or species differences. It is concluded that if endogenous cortisol production is blocked by metyrapone, the reactions occurring as a result of the endotoxin-induced acute lung injury and shock are greatly enhanced and that therefore pretreatment with metyrapone might be an important addition to this model with specific pathogen-free pigs.

Topics: Acid-Base Imbalance; Animals; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Endothelin-1; Endotoxins; Female; Hydrocortisone; Hypotension; Interleukin-8; Leukocytes; Male; Metyrapone; Neutrophils; Nitric Oxide; Nitrites; Peroxidase; Proteins; Pulmonary Edema; Respiratory Distress Syndrome; Respiratory Function Tests; Shock; Specific Pathogen-Free Organisms; Swine; Tumor Necrosis Factor-alpha

Elevated tumor necrosis factor serum levels have been reported in patients with severe congestive heart failure. This study was designed to characterize the cytokine profile in patients with acute circulatory collapse.. Blood drawn from 14 consecutive patients within 24 hours before undergoing left ventricular assist device placement and after at least 30 days of mechanical assistance or before transplantation was assayed for levels of interleukin 6, interleukin 8, and tumor necrosis factor-alpha.. Interleukin 6 level was elevated in 11 (79%), interleukin 8 in 10 (71%), and tumor necrosis factor in 2 (14%) of the 14 patients. After hemodynamic recovery, interleukin 6 levels decreased from 33.6 +/- 9 pg/mL to 11.3 +/- 4 pg/mL (p = 0.05) and interleukin 8 levels decreased from 122 +/- 34 pg/mL to 19.7 +/- 8 pg/mL (p = 0.005). Tumor necrosis factor-alpha levels did not vary significantly; they were associated with infection in 2 left ventricular assist device recipients and normalized after left ventricular assist device support. All patients had resolution of circulatory shock after mechanical support and had improvement in parameters of end-organ function.. Circulatory shock treated with left ventricular assist device placement is associated with a proinflammatory response similar to that seen in septic shock. The decrease in cytokine serum levels that follows hemodynamic recovery suggests that these cytokines may be markers of tissue damage and may modulate cardiac dysfunction.

Topics: Biomarkers; Female; Follow-Up Studies; Heart-Assist Devices; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Resuscitation; Shock; Tumor Necrosis Factor-alpha

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