interleukin-8 and Burns

Excessive systemic inflammatory response remains as a major problem underlying severe burns. This study aimed to assess the effect of low-dose glucocorticoid treatment in downregulating systemic inflammation in severely burned patients.. A prospective study from 2001 to 2014 at our hospital was conducted to compare the patients who received low-dose glucocorticoid during the acute phase with those who did not. Patients with burns 70% or greater of their total body surface area were included, and their plasma levels of inflammatory cytokines and clinical outcomes were compared.. A total of 69 patients were included in this study, with 31 patients receiving glucocorticoid treatment and the others not. Patient demographics including age, burn size, and incidence of inhalation injury were similar in both groups. The incidence of pulmonary infection and stress ulcer (and/or hemorrhage) was 24.2% and 3.0% in the treatment group, respectively, significantly lower than 47.8% and 19.6% of the control group (P < .05). Length of hospital stay was almost 13 days shorter in the treatment group (P < .05), whereas there was no significant difference in the overall mortality, duration of mechanical ventilation, and incidence of sepsis between the 2 groups. The enzyme-linked immunosorbent assay results confirmed that the plasma levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-8 were significantly lower in the treatment group (P < .05).. Low dose of glucocorticoid treatment during the acute phase could reduce the levels of proinflammatory cytokines in severely burned patients and subsequently decrease the incidence of pulmonary infection and stress ulcer, as well as the length of hospital stay.

Topics: Adult; Anti-Inflammatory Agents; Burns; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Glucocorticoids; Humans; Incidence; Inflammation; Interleukin-6; Interleukin-8; Length of Stay; Male; Middle Aged; Pneumonia; Prospective Studies; Sepsis; Stomach Ulcer; Treatment Outcome; 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

In select burn intensive care units, high-frequency percussive ventilation is preferentially used to provide mechanical ventilation in support of patients with acute lung injury, acute respiratory distress syndrome, and inhalation injury. However, we found an absence of prospective studies comparing high-frequency percussive ventilation with contemporary low-tidal volume ventilation strategies. The purpose of this study was to prospectively compare the two ventilator modalities in a burn intensive care unit setting.. Single-center, prospective, randomized, controlled clinical trial, comparing high-frequency percussive ventilation with low-tidal volume ventilation in patients admitted to our burn intensive care unit with respiratory failure.. A 16-bed burn intensive care unit at a tertiary military teaching hospital.. Adult patients ≥ 18 yrs of age requiring prolonged (> 24 hrs) mechanical ventilation were admitted to the burn intensive care unit. The study was conducted over a 3-yr period between April 2006 and May 2009. This trial was registered with ClinicalTrials.gov as NCT00351741.. Subjects were randomly assigned to receive mechanical ventilation through a high-frequency percussive ventilation-based strategy (n = 31) or a low-tidal volume ventilation-based strategy (n = 31).. At baseline, both the high-frequency percussive ventilation group and the low-tidal volume ventilation group had similar demographics to include median age (interquartile range) (28 yrs [23-45] vs. 33 yrs [24-46], p = nonsignificant), percentage of total body surface area burn (34 [20-52] vs. 34 [23-50], p = nonsignificant), and clinical diagnosis of inhalation injury (39% vs. 35%, p = nonsignificant). The primary outcome was ventilator-free days in the first 28 days after randomization. Intent-to-treat analysis revealed no significant difference between the high-frequency percussive ventilation and the low-tidal volume ventilation groups in mean (± sd) ventilator-free days (12 ± 9 vs. 11 ± 9, p = nonsignificant). No significant difference was detected between groups for any of the secondary outcome measures to include mortality except the need for "rescue" mode application (p = .02). Nine (29%) in the low-tidal volume ventilation arm did not meet predetermined oxygenation or ventilation goals and required transition to a rescue mode. By contrast, two in the high-frequency percussive ventilation arm (6%) required rescue.. A high-frequency percussive ventilation-based strategy resulted in similar clinical outcomes when compared with a low-tidal volume ventilation-based strategy in burn patients with respiratory failure. However, the low-tidal volume ventilation strategy failed to achieve ventilation and oxygenation goals in a higher percentage necessitating rescue ventilation.

Topics: Adult; Burns; Female; Granulocyte-Macrophage Colony-Stimulating Factor; High-Frequency Ventilation; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Respiration, Artificial; Tidal Volume; Treatment Outcome; Tumor Necrosis Factor-alpha; Ventilator Weaning; Young Adult

To investigate the influence of continuous renal replacement therapy (CRRT) on the plasma levels of endotoxin and cytokines in severely burned patients with sepsis.. Ten burn patients who received CRRT and another 10 without CRRT were investigated in terms of the changes in their plasma concentrations of endotoxin and some cytokines (TNFalpha, IL-1beta, IL-6, IL-8).. The plasma concentrations of endotoxin and all the cytokines (TNFalpha, IL-1beta, IL-6, IL-8) after CRRT treatment were significantly lower than those before the treatment (P < 0.01), and the plasma levels of the above factors at all the time points after CRRT treatment than those in patients were evidently lower by routine treatment (P < 0.05 - 0.01).. CRRT treatment could effectively lower the plasma levels of endotoxin and some cytokines (TNFalpha, IL-1beta, IL-6, IL-8).

Topics: Burns; Endotoxins; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Renal Replacement Therapy; Sepsis; Tumor Necrosis Factor-alpha

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

Acquired neutrophil dysfunction is considered an important cause of increased susceptibility to infection in patients with burns. In the early postinjury phase, large amounts of circulating chemo-attractants, cytokines and endotoxins induce strong systemic activation of neutrophils which may impair their motile functions. Actin is the most prevalent component of the microfilament lattice that generates force for the neutrophil motile responses, and in the present study we examined the dynamics of actin polymerization and depolymerization in neutrophils from 11 patients with large burns. At admission, the amount of polymerized actin in unstimulated neutrophils was 39.9 per cent higher than that of parallel controls. In addition, there was a positive correlation between the amount of polymerized actin and the total body surface area (TBSA) burn. The time course of patient neutrophil actin polymerization in response to FMLP, C5a, (Ser-IL-8)72, (Ala-IL-8)77 and crosslinking of surface Fc gamma RII was similar to that of controls, and the maximal amount of neutrophil F-actin was demonstrated after 30 s stimulation. At the peak of actin polymerization, however, patient neutrophils contained 27.3, 24.0, 24.7 and 25.6 per cent more polymerized actin than control cells stimulated with FMLP, (Ser-IL,-8)77, (Ala-8)77 and Fc gamma RII crosslinking, respectively. However, the relative increase of neutrophil F-actin following stimulation was significantly lower in patients than in controls. Moreover, the rate of patient neutrophil actin depolymerization was 39.0, 23.5, 63.3 and 51.7 per cent lower than that of controls after stimulation with FMLP, C5a (Ser-IL-8)72 and Fc gamma RII crosslinking, respectively. At discharge, the dynamics of neutrophil actin polymerization and depolymerization were similar to that of controls. The results demonstrate that in neutrophils during the early postburn phase, there are increased basal levels of polymerized actin, a lower responsiveness to stimulation and a reduced rate of actin depolymerization. As periodic polymerization and depolymerization of actin is essential for all neutrophil motile responses, it is probable that the alterations observed may contribute significantly to the overall neutrophil dysfunction following thermal injury.

Topics: Actins; Adult; Aged; Biopolymers; Burns; Cells, Cultured; Complement C5a; Cross-Linking Reagents; Female; Flow Cytometry; Humans; Interleukin-8; Male; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils

Endotoxin as the inciting agent of cytokines and other mediators, whose high level expression correlates with the septic shock and MOF, has been the one of leading causes of death in ICU.. For treating sepsis and MOF caused by endotoxin, the anti-lipid A of LPS antibody was used, 19 burned patients whose TBSA varied from 50% to 100% were divided into anti-LPS treatment group and nontreated group.. The levels of serum endotoxin, IL-6, IL-8, TNF and soluble IL-2R were lower obviously in patients of anti-LPS group than those of nontreated group (P < 0.05).. Clinical study surggests that anti-lipid A of LPS antibody can act as an therapeutic agent against gram-negative bacterin infection in burned patients.

Topics: Adult; Antibodies; Antitoxins; Burns; Cytokines; Endotoxemia; Endotoxins; Female; Humans; Interleukin-6; Interleukin-8; Lipid A; Male; Tumor Necrosis Factor-alpha

Diabetes is involved in delayed wound healing that can be cured by natural products such as garlic, turmeric, and fibroin extracts. Alloxan monohydrate is used for inducing diabetes in mice. The percent wound contraction of garlic (150 mg/ml), turmeric (100 mg/ml), and fibroin (50 mg/ml), individually and in combinations garlic (150 mg/ml) + fibroin (50 mg/ml), turmeric (100 mg/ml) + fibroin (50 mg/ml), garlic (150 mg/ml) + turmeric (100 mg/ml), and garlic (150 mg/ml) + turmeric (100 mg/ml) + fibroin (50 mg/ml) was checked by evaluating the healing time, % wound contraction and histological analysis. The serum level of MMPs (MMP 2, MMP7, MMP 9), pro-inflammatory cytokines (TNF-α, IL-6, IL-8), and TIMPs were evaluated. With the combination of three extracts (Ga+Tu+Fi) garlic (150 mg/ml), turmeric (100 mg/ml) and fibroin (50 mg/ml), wounds healed in 12 days and had 97.3 ± 2.2% wound contraction. While the positive control (polyfax) and diabetic control (saline) wounds healed in 17- and 19-days with wound contraction of 96.7 ± 1.4% and 96.3 ± 1.1%, respectively. Histological analysis showed that the combination of Ga+Tu+Fi exhibited an increase in the growth of collagen fibers, fibroblasts number, and keratinocytes, and lessened inflammation of blood vessels. The combination of Ga+Tu+Fi significantly alleviated the serum concentration of TNF-α (14.2 ± 0.7 pg/ml), IL-6 (10.0 ± 1.0 pg/ml), IL-8 (16.0 ± 1.5 pg/ml), MMP2 (228.0 ± 18.1 pg/ml), MMP7 (271.0 ± 9.9 pg/ml), and MMP9 (141.0 ± 5.3 pg/ml) to diabetic control. The level of TIMPs (193.0 ± 9.1 pg/ml) was increased significantly with respect to diabetic control. We conclude that the combination of these biomaterials possessed high regenerative and healing capabilities and can be an effective remedy in the healing of chronic wounds in diabetic patients.

Topics: Animals; Burns; Curcuma; Diabetes Mellitus; Fibroins; Garlic; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 7; Mice; Tumor Necrosis Factor-alpha; Wound Healing

Thermal injury often leads to prolonged and excessive inflammation, which hinders the recovery of patients. There is a notable absence of suitable animal-free models for investigating the inflammatory processes following burn injuries, thereby impeding the development of more effective therapies to improve burn wound healing in patients.. In this study, we established a human full skin equivalent (FSE) burn wound model and incorporated human peripheral blood-derived monocytes and T cells.. Upon infiltration into the FSEs, the monocytes differentiated into macrophages within a span of 7 days. Burn-injured FSEs exhibited macrophages with increased expression of HLA-DR. Collectively, this study represents a significant advancement in the development of an immunocompetent human skin model, specifically tailored for investigating burn-induced innate or adaptive immune reactions at the site of burn injury.

Topics: Burns; Cytokines; Humans; Interleukin-8; Monocytes; T-Lymphocyte Subsets

Burn injuries are the most frequent injuries in the world, with a death rate of 2.3-3.6%. Children and people of working age constitute 85-90% of the burn cases. Burn injury results in metabolic problems, a generalized inflammatory response, inefficient energy use, and other physiological alternations that may cause organ and system dysfunction and sepsis. Sepsis is mostly caused by multiple organ failures and has unique characteristics in burn injuries, which make it the most dangerous complication of burn injuries. This study aimed to investigate the correlation between sepsis in burn patients and the level of interleukin 8 (IL-8) in their serum. In total, 60 patients with burn injuries were included in this study. Blood samples were obtained from 60 burn patients and 30 healthy individuals as controls. The BacT/Alert and Vitek2 systems were used to identify the bacteria and determine their susceptibility to these bacteria. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to determine IL-8 serum levels. Based on the results, elevated levels of IL-8 were observed in the serum of burn patients, compared to healthy individuals. Concentration of IL-8 was significantly higher in patients with sepsis, compared to healthy individuals without sepsis.

Topics: Burns; Child; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-6; Interleukin-8; Sepsis

In current intensive care treatment, some patients with severe burns cannot be saved due to progressive organ failure. Further investigation of the pathogenesis of severe burns is needed to improve the mortality rate. In burns, inflammatory cytokines form a network that leads to an inflammatory response. Adipocytes secrete physiologically active substances (adipokines). The roles of adipokines have not been completely clarified in burn patients. This study aimed to determine the relation between serial changes of adipokines and clinical course in severely burned patients.. This was a single-center, retrospective, observational study. Patients' blood samples were collected on the day of injury and around 1 week later. Adipokines (adiponectin, angiotensinogen, chemerin, CXCL-12/SDF-1, leptin, resistin, vaspin, visfatin), various inflammatory cytokines, syndecan-1 and C1 esterase inhibitor were measured.. Thirty-eight patients were included. Resistin levels were significantly higher in the non-survivors versus survivors on Day 1 after burn injury. Hierarchical clustering analysis showed common clusters on Day 1 and at 1 Week after burn injury (resistin, IL-6, IL-8, IL10 and MCP-1). The correlation coefficient of resistin to SOFA score at 1 Week was significant. Logistic regression analysis showed a significant relation of resistin levels on Day 1 with prognosis; the area under the ROC curve for resistin was 0.801.. In the acute phase of burns, resistin was associated with other pro-inflammatory cytokines and was related to the severity and prognosis of major burns.

Topics: Adipokines; Adiponectin; Angiotensinogen; Burns; Complement C1 Inhibitor Protein; Cytokines; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Leptin; Nicotinamide Phosphoribosyltransferase; Prognosis; Resistin; Retrospective Studies; Syndecan-1

There are few studies on the inflammatory processes and the role of cytokines involved in pediatric burn injuries. The present study aims to measure the serum levels of cytokines and their relationship with the degree of burn injury in children. Within the 48 hours of hospitalization, the serum samples were obtained to measure inflammatory cytokines (interleukin-6, interleukin-8, interleukin-10 [IL-6, IL-8, and IL-10] and tumor necrosis factor-alpha [TNF-α]). The level of all of these cytokine factors was assessed by enzyme-linked immunosorbent assay technique. The mean levels of IL-6, IL-8, IL-10, and TNF-α was 18.15 ± 4.77 pg/ml, 59.54 ± 4.59 pg/ml, 8.41 ± 2.09 pg/ml, and 1.48 ± 0.15 pg/ml, respectively, which were higher than the normal range designated for the healthy pediatrics age group. The levels of TNF-α were higher in patients with sepsis (P = .03) and deceased patients (P = .001). There was a statistically significant difference in the levels of IL-8 in patients with second- (.001) and third-degree (.001) burn injuries in comparison to the first-degree burn injuries, and the level of IL-8 was statistically significantly higher in patients with electrical burn injuries in comparison to scald burn injuries (.01). IL-10 was statistically significantly higher in patients with contact burn injuries in comparison to scald (.001) and flame (.03) burn injuries. Cytokine levels in pediatric burn patients increased after severe burn injuries. There was a significant correlation between the levels of IL-8 and the degree of burn injuries.

Topics: Body Surface Area; Burns; Child; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Tumor Necrosis Factor-alpha

Hemodynamic aberrations after severe burns are treated with aggressive intravenous (IV) fluid resuscitation however, oral resuscitation has been proposed in resource poor scenarios. Previously we have shown that animals receiving oral fluid following burns were able to recover kidney function. However, immune function such as circulating and splenic immune cell populations after oral or intravenous fluid administration was not examined. Herein, we perform a follow up analysis of splenic tissue and plasma from the previous animal study to examine the splenic response following these resuscitation strategies after burn injury.. Eighteen anesthetized Yorkshire swine receiving 40%TBSA contact burns were randomized to receive either: (1) no fluids (Fluid Restricted; negative control), (2) 70 mL/kg/d Oral Rehydration Salt solution (Oral), or (3) 2 mL/kg/%TBSA/d of lactated Ringer's solution IV. Blood was drawn for blood cell analysis, and CT scans were performed before and 48 h post-burn, at which point spleens were harvested for histological, Western blot, and RT-PCR analyses.. Splenic artery diameter decreased by -0.97 ± 0.14 mm in fluid-restricted animals, while IV led to an increase of 0.68 ± 0.30 mm. No significant differences were detected in white and red pulp. IV fluids reduced the population of splenic monocytes (CD163; P = 0.001) and neutrophils (MPO protein; P = 0.13), as well as cytokines IL-8 (P = 0.003), IFN-γ (P = 0.11) and TNFα (P = 0.05). Additionally, withholding IV fluids consistently decreased the expression of FoxP3, CCR6, and IL17β in spleen, suggesting a shift in T-cell phenotype with IV resuscitation.. The route of fluid administration has a minor influence on the changes in circulating and splenic leukocytes post-burn in the acute phase. Further research is needed to help guide resuscitation approaches using immunologic markers of splenic function following burns.

Topics: Administration, Intravenous; Administration, Oral; Animals; Burns; Fluid Therapy; Forkhead Transcription Factors; Immunophenotyping; Interferon-gamma; Interleukin-17; Interleukin-8; Leukocyte Count; Leukocytes; Lymphocyte Count; Monocytes; Neutrophils; Organ Size; Real-Time Polymerase Chain Reaction; Receptors, CCR6; Resuscitation; Spleen; Splenic Artery; Sus scrofa; T-Lymphocytes; Tumor Necrosis Factor-alpha

Silver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag. Twenty patients with an average burned body surface area of 27.68% were included in this study.. Patients' Ag. These findings suggest that Ag

Topics: Adult; Anti-Infective Agents, Local; Apoptosis; Body Surface Area; Burns; Cell Survival; Female; Humans; In Vitro Techniques; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Neutrophils; Reactive Oxygen Species; Silver; Silver Nitrate; Silver Sulfadiazine; Tumor Necrosis Factor-alpha

Inhalation injury commonly accompanies thermal injury, increasing the likelihood of mortality and multiple organ dysfunction (MOD). Large animal models have given important insight into the pathophysiology of this injury; however recapitulating late MOD has remained difficult. The current report describes experiments using a smoke inhalation and burn model, with follow-up of ambulatory swine for 14days with bronchoscopy, CT scanning, and bronchoalveolar lavage fluid (BALF)/blood collection. Clinically, animals cleared airway damage in the first several days after-injury. This was mirrored with erythematous airways on day 2 after-injury, which resolved by the end of the experiment, as did parenchymal damage seen on CT. An initial rise in the protein content of BALF immediately after-injury was followed by a dramatic increase in the concentration of leukocytes. Circulating neutrophils increased while lymphocytes decreased; both correlated with cell counts in BALF. IL8 levels in BALF increased 30-fold and remained elevated throughout the experiment. IL1ra increased circulation immediately after-injury, and afterwards in BALF. Other cytokines (TNFα, IL12) transiently increased in BALF (and decreased in circulation) on day 2. Taken together, these results display a remarkable capability for the lungs to recover in the absence of intubation, with further evidence of the role of cytokines such as IL8 and IL1ra. The possible exacerbating effects of clinical practices such as ventilation and bronchoscopies should be considered.

Topics: Animals; Bronchoalveolar Lavage Fluid; Bronchoscopy; Burns; Cytokines; Disease Models, Animal; Female; Interleukin 1 Receptor Antagonist Protein; Interleukin-12; Interleukin-8; Lung; Recovery of Function; Respiration, Artificial; Respiratory Distress Syndrome; Smoke Inhalation Injury; Sus scrofa; Swine; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha; Wound Healing

Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300μm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (p<0.05) in burn injured wounds. Histological analysis supported objective clinical findings with marked scar-like collagen proliferation within the dermis, increased vascular density, and prolonged and increased cellular infiltration. Observed differences in contracture also correlated with earlier and more prominent myofibroblast differentiation as demonstrated by α-SMA staining. Antecedent thermal injury worsens split-thickness skin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been demonstrated. Future research to enhance quality of skin replacement therapies should be directed toward modulation of inflammation and assessments for complete excision.

Topics: Actins; Animals; Burns; Cicatrix; Contracture; Disease Models, Animal; DNA Fragmentation; Female; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Interleukin-1beta; Interleukin-8; Matrix Metalloproteinase 1; Neovascularization, Pathologic; Real-Time Polymerase Chain Reaction; Skin; Skin Transplantation; Sus scrofa; Swine; Transplants

For a long time iodine has been used as an active dermal agent in the treatment of inflammatory, immune-mediated and infectious diseases. Moreover, topical iodine application has been reported to provide protection against sulfur-mustard-induced skin lesions, heat-induced and acid-induced skin burns in both haired guinea-pigs and mouse ear swelling models. However, the exact mechanism of action underlying these benefits of iodine has not yet been elucidated. In the current study, a novel mechanism of action by which iodine provides skin protection and relief, based on its electrophilic nature, is suggested. This study demonstrates that both iodine and iodide are capable of activating the Nrf2 pathway in human skin. As a result, skin protection against UVB-induced damage was acquired and the secretion of pro-inflammatory cytokines (IL-6, IL-8) from LPS-challenged skin was reduced. Iodide role in the enhanced activation of this pathway is demonstrated. The mode of action by which iodine and iodide activate the Nrf2 pathway is discussed.

Topics: Administration, Topical; Animals; Burns; Disease Models, Animal; Humans; Inflammation; Interleukin-6; Interleukin-8; Iodides; Iodine; Mice; Mustard Gas; NF-E2-Related Factor 2; Skin; Ultraviolet Rays

Patients with severe burns often develop acute lung injury (ALI), systemic inflammatory response syndrome (SIRS) often complicates with ALI. Sivelestat sodium hydrate is an effective drug against ALI. However, the mechanisms of this beneficial effect are still poorly understood. In the current study, we evaluate the effects of sivelestat sodium hydrate on systemic and local inflammatory parameters (neutrophil elastase [NE], interleukin [IL]-8, matrix metalloproteinase [MMP] 2 and 9) in a rat model of severe burns and ALI. And to analyze the correlations between expression of NE and IL-8 and acute lung injury.. 48 Sprague-Dawley (SD) rats were divided into 3 groups: normal control group, severe burns injury group and severe burns treated with sivelestat sodium hydrate group (SSI). The lung water content and PaO2 were detected in each group. Pathological manifestations in each group were observed for pathology scoring in SD rats with acute lung injury. ELISA was used for detecting expression of NE and IL-8 in serum and BAL specimens of SD rats in each group. RT-PCR was used to detect mRNA expression of NE and IL-8 in lung tissues of each group. Western blotting was used for detecting protein expression of MMP-2 and MMP-9 in lung tissues of each group. SPSS 18.0 was used for statistical analysis.. The PaO2 was significantly increased after sivelestat sodium hydrate intravenous injection. Pathological score and water content of lung tissue were significantly decreased in SSI group compared with severe burns injury group, slightly higher than that normal control group. NE and IL-8 levels significantly decreased in serum, BAL and lung tissue specimens after sivelestat sodium hydrate intravenous injection; Expression of MMP-2 and MMP-9 were significantly up-regulated in severe burns group and showed no significantly changed after sivelestat sodium hydrate intravenous injection.. In a rat model of severe burns and ALI, administration of sivelestat sodium hydrate improved symptoms of ALI and significantly decreased inflammatory parameters NE and IL-8.

Topics: Acute Lung Injury; Animals; Blood Gas Analysis; Burns; Disease Models, Animal; Glycine; Inflammation Mediators; Interleukin-8; Leukocyte Elastase; Lung; Rats; Rats, Sprague-Dawley; Sulfonamides; Systemic Inflammatory Response Syndrome

Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute respiratory distress syndrome (ARDS). Some lung-protective ventilation strategies, such as low tidal volume, are associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of high-frequency percussive ventilation (HFPV) to patients with respiratory distress after smoke inhalation injury influenced initial biomarker levels of lung injury (just before and after using percussive ventilation).. A prospective observational cohort study was conducted in the intensive care unit of the Brussels Burn Center. Fifteen intubated, mechanically ventilated patients with minor burns and ARDS following smoke inhalation were enrolled in our study. Physiologic data and serum samples were collected before intubation and at four different time points within the first 48h after intubation to measure the concentration of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF alpha). The differences in biomarker levels before and after starting HFPV were analyzed using repeated measure analysis of variance and a paired t test with correction for multiple comparisons.. Before starting HFPV under endotracheal intubation, all biological markers (IL-6, IL-8, and TNF alpha) were elevated in the spontaneously breathing patients with acute lung injury (ALI). After intubation and institution of a positive pressure ventilation with HFPV (tidal volume 5.6-6.6ml/kg per ideal body weight), none of the biological markers were increased significantly at either an early (3±2h) or a later point in time. However, the levels of IL-8 had decreased significantly after intubation at a later point in time. During the post-intubation period, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio increased significantly and the plateau airway pressure decreased significantly.. Levels of IL-6, IL-8, and TNF alpha are elevated in spontaneously ventilating patients with minor burns and ARDS following smoke exposition prior to endotracheal intubation. The institution of HFPV with percussive positive pressure ventilation enhances blood oxygenation and could not further increase the initial levels of these biological markers of lung injury after smoke inhalation injury.

Topics: Adult; Biomarkers; Burn Units; Burns; Cohort Studies; Female; High-Frequency Ventilation; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Positive-Pressure Respiration; Prospective Studies; Respiratory Distress Syndrome; Smoke Inhalation Injury; Tidal Volume; Tumor Necrosis Factor-alpha; Ventilator-Induced Lung Injury; Young Adult

At all stages of wound healing, growth factors and cytokines play a particularly important role in the interaction with keratinocytes cellular receptors. Keratinocytes have received little attention about their potential to act as a source and target of cytokines. Changes in the cytokine levels after the burning occur prior to the metabolic abnormalities. Thus, it may be possible to develop therapeutic interventions that can mitigate the acute inflammatory response and modulating expression of these cytokines. The objective was to evaluate the expression of 84 genes mediators of the inflammatory response by using PCR array in a primary human epidermal cultured keratinocytes from patients with burns.. Keratinocytes cultured from normal skin around injury from small and large burn patient were treated for DNA synthesis. The samples were analyzed by the PCR Superarray(®) assay and curve analyses were performed for 84 relevant human genes and their involvement in the inflammatory cytokines pathway and receptors. These genes were checked for the up or down regulation. And it was used MetaCore™ for the analysis of networks and Gene Ontology (GO) processes.. Chemokines of the CXC family were more expressed in the large burn group, except CXCL12. The C, CC and CX3C chemokine family were downregulated, especially in the small burn group. The interleukins IL8 and IL1B were more expressed in large burn than in small burn; except IL13RA1, IL13 and IL5RA that were downregulated, mainly in the small burn group.. The cytokine profile showed some important differences between the large and small burn patients, and from this original database, we can create new interventional trials in acute inflammation in burns.

Topics: Adult; Burns; Case-Control Studies; Cells, Cultured; Chemokines, C; Chemokines, CC; Chemokines, CXC; Cytokines; Down-Regulation; Female; Gene Expression Profiling; Humans; Inflammation; Inflammation Mediators; Interleukin-13; Interleukin-13 Receptor alpha1 Subunit; Interleukin-1beta; Interleukin-5 Receptor alpha Subunit; Interleukin-8; Keratinocytes; Male; Severity of Illness Index; Transcriptome; Up-Regulation; Wound Healing

To observe and study the effects of sivelestat on acute lung injury in dogs with severe burn-blast combined injury.. Thirty-two male beagle dogs of clean grade were divided into 4 groups: uninjured group (U), combined injury control group (CIC), combined injury+low dose of sivelestat group (CI+LS), combined injury+high dose of sivelestat group (CI+HS), with 8 dogs in each group. Except for the dogs in group U which were not injured, the dogs in the other 3 groups were inflicted with severe burn-blast combined injury. According to the Parkland formula, the dogs in groups U and CIC were infused with physiological saline, and the dogs in groups CI+LS and CI+HS received sivelestat with the dosage of 0.5 and 2.0 mg·kg(-1)·h(-1) respectively in addition. The 24 h continuous intravenous infusion was carried out for 2 days. At post injury hour (PIH) 6, CT scanning was conducted to observe the lung damage. At PIH 2, 6, 12, 24, and 48, mean arterial pressure (MAP), respiratory rate (RR), extra vascular lung water (EVLW), pulmonary vascular permeability index (PVPI), PaO2, and PaCO2 were measured; the contents of neutrophil elastase (NE), IL-8, and TNF-α were determined by ELISA. At PIH 48, all the dogs were sacrificed, and the lung tissues were harvested to measure the wet to dry lung weight ratio. The same examination was carried out in the dogs of the group U at the same time points. Data were processed with analysis of variance of repeated measurement and LSD test.. (1) CT images showed some exudative lesions in the dogs of groups CIC and CI+LS but not in the dogs of groups U and CI+HS. (2) No statistically significant differences were observed in MAP at each time point between every two groups (with P values above 0.05). The RR values in group U were significantly different from those of the other 3 groups at all time points (with P values below 0.05). The values of EVLW and PVPI in 3 combined injury groups were significantly different from those in group U at PIH 6, 12, 24, and 48 (with P values below 0.05). The values of RR and EVLW in group CI+LS were significantly different from those in group CI+HS at PIH 12, 24, and 48 (with P values below 0.05). The values of PVPI in group CI+LS were significantly different from those in group CI+HS at PIH 24 and 48 (with P values below 0.05). (3) The levels of PaO2 and PaCO2 showed significant differences between group U and the other 3 groups at each time point (with P values below 0.05). The levels of PaO2 in group CI+LS were significantly different from those in CI+HS group at PIH 12, 24, and 48 (with P values below 0.05). The level of PaCO2 showed significant differences between group CI+LS and group CI+HS at PIH 24 and 48 (with P values below 0.05). (4) The contents of NE (except for PIH 2), TNF-α, and IL-8 showed significant differences between group U and the other 3 groups at each time point (P < 0.05 or P < 0.01). At PIH 2, 6, 12, 24, and 48, the contents of NE in groups U, CIC, CI+LS, and CI+HS were respectively (69 ± 21), (83 ± 24), (80 ± 20), (75 ± 17), (72 ± 27) pg/mL; (66 ± 24), (196 ± 20), (231 ± 26), (252 ± 25), (266 ± 22) pg/mL ; (71 ± 22), (180 ± 27), (214 ± 21), (194 ± 24), (218 ± 20) pg/mL; (68 ± 22), (136 ± 24), (153 ± 22), (146 ± 26), (150 ± 28) pg/mL. NE values in group CI+HS were statistically different from those in groups CIC and CI+LS at PIH 6, 12, 24, and 48 (with P values below 0.05). The contents of TNF-α in group CI+LS were statistically different from those in groups CIC and CI+HS at PIH 24 and 48 (with P values below 0.05). The contents of IL-8 in group CI+LS were statistically different from those in group CI+HS at PIH 24 and 48 (with P values below 0.05). (5) At PIH 48, the wet to dry lung weight ratio of group CIC was statistically different from that in group CI+LS or group CI+HS (with P values below 0.05); there was also difference between group CI+LS and group CI+HS (P < 0.05).. Sivelestat, especially in a high dose, exerts a protective effect in acute lung injury after burn-blast combined injury through improving the index of blood gas analysis, ameliorating pulmonary edema, and lowering the production of pro-inflammatory mediators.

Topics: Acute Lung Injury; Animals; Blood Gas Analysis; Burns; Capillary Permeability; Dogs; Extravascular Lung Water; Glycine; Infusions, Intravenous; Interleukin-8; Male; Pulmonary Edema; Serine Proteinase Inhibitors; Sulfonamides; Tumor Necrosis Factor-alpha

To observe the effects of blood purification in the treatment of burn sepsis, in order to provide evidence for its application.. Twenty-seven patients with burn sepsis admitted to our burn ward from June 2012 to December 2013, conforming to the study criteria, were divided into conventional treatment group (CT, n = 15) and blood purification group (BP, n = 12) according to the random number table. After the diagnosis of sepsis was confirmed, patients in group CT received CT, while patients in group BP received both CT and continuous veno-venous hemodiafiltration for 48 hours. At the time of diagnosis of sepsis (before treatment) and post treatment hour (PTH) 24 and 48, levels of blood lactate and PaO2 were analyzed with blood gas analyzer, and the oxygenation index (OI) was calculated; blood sodium, blood glucose, blood urea nitrogen (BUN), creatinine, white blood cell count (WBC), procalcitonin (PCT) were determined; acute physiology and chronic health evaluation (APACHE) II score was estimated basing on the body temperature, respiratory rate, mean arterial pressure, PaO2, and blood pH values. The levels of TNF-α, IL-8, and IL-6 in serum were determined by ELISA. Data were processed with Fisher's exact test, t test, analysis of variance for repeated measurement, LSD- t test, and LSD test.. (1) The levels of blood lactate of patients in group BP were significantly lower than those of group CT at PTH 24 and 48 (with t values respectively 1.62 and 2.44, P values below 0.05). Compared with that detected before treatment, the level of blood lactate in group BP was significantly decreased at PTH 48 (P < 0.05). The OI values of patients in group BP at PTH 24 and 48 [(247 ± 30), (288 ± 41) mmHg, 1 mmHg = 0.133 kPa] were significantly higher than those of group CT [(211 ± 32), (212 ± 30) mmHg, with t values respectively 3.02 and 5.63, P values below 0.01]. Compared with that detected before treatment, the OI values of patients in group BP at PTH 24 and 48 were significantly higher (P values below 0.01). (2) Compared with those of group CT at PTH 24 and 48, the levels of blood sodium, BUN, and creatinine were significantly lower (with t values from 1.74 to 6.75, P < 0.05 or P < 0.01), while the level of blood glucose was approximately the same (with t values respectively -0.92, -0.38, P values above 0.05) in group BP. Compared with those detected before treatment, the levels of blood sodium, BUN, and creatinine of group BP at PTH 24 and 48 were significantly lower (P < 0.05 or P < 0.01). (3) The levels of WBC and PCT of patients in group BP at PTH 24 and 48 were significantly lower than those of group CT (with t values from 2.11 to 6.63, P < 0.05 or P < 0.01). Compared with those detected before treatment, the levels of WBC and PCT of patients in group BP at PTH 24 and 48 were significantly lower (P < 0.05 or P < 0.01). (4) The APACHE II scores of patients in group BP at PTH 24 and 48 [(18.7 ± 2.6) and (16.7 ± 3.0) scores] were significantly lower than those of group CT [(23.1 ± 1.6) and (25.5 ± 1.6) scores, with t values respectively 5.44 and 9.87, P values below 0.01]. Compared with those calculated before treatment, the APACHE II scores of patients in group CT were significantly increased (P < 0.05 or P < 0.01), while those in group BP were decreased at PTH 24 and 48 (P < 0.05 or P < 0.01). (5) The levels of TNF-α, IL-6, and IL-8 in serum of patients in group BP at PTH 24 and 48 were significantly lower than those of group CT (with t values from 6.12 to 19.78, P values below 0.01). Compared with those detected before treatment, the levels of TNF-α, IL-6, and IL-8 in serum of group BP at PTH 24 and 48 were significantly decreased (with P values below 0.01).. BP+CT is effective in improving organ function, correcting the disorder of internal environment, and controlling inflammation. Therefore, BP is an important method in the treatment of burn sepsis.

Topics: Aged; Animals; Blood Gas Analysis; Burns; Humans; Interleukin-6; Interleukin-8; Sepsis; Serum; Tumor Necrosis Factor-alpha

High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer's solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1 expression.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Burns; Butyric Acid; Female; Granulocyte Colony-Stimulating Factor; HMGB1 Protein; Inflammation; Interleukin-3; Interleukin-8; Lung; Malondialdehyde; Neutrophil Infiltration; Oxidative Stress; Peroxidase; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Tumor Necrosis Factor-alpha

Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which is important in normal physiology and disease. In the present study, the involvement of H2S in the regulation of the immune response induced by burn injury was investigated in mice. Adult male C57BL/6 mice were subjected to burn injuries and treated with vehicle (0.9% sodium chloride, NaCl; 100 ml/kg body weight; subcutaneously, s.c.) or the H2S donor (sodium hydrosulfide, NaHS; 2 mg/kg body weight; s.c.). Compared with the controls, mice which received burn injuries exhibited a significant decrease in plasma H2S levels. Moreover, the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8 significantly increased, while IL‑10 levels were decreased, compared with that of the controls in the plasma of mice subjected to burn injuries. Myeloperoxidase (MPO) activity in the liver tissue of injured mice was also markedly higher compared with that of the control group. However, the administration of NaHS significantly decreased the levels of TNF‑α, IL‑6 and IL‑8 but increased the levels of IL‑10 in the plasma of mice subjected to burn injuries. In addition, the MPO activity was decreased by NaHS. These results suggested that H2S regulates the inflammatory response induced by burn injury by modulating the levels of TNF‑α, IL‑6, IL‑8 and IL‑10. Thus, it was proposed that the administration of the H2S donor, NaHS, may be a useful therapy against the exaggerated immune response that is associated with burn injury.

Topics: Animals; Anti-Inflammatory Agents; Burns; Hydrogen Sulfide; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Liver; Male; Mice; Mice, Inbred C57BL; Peroxidase; Sulfides; 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

Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats.. One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury.. In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes.. Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8.

Topics: Animals; Blast Injuries; Bronchoalveolar Lavage Fluid; Burns; Carbon Dioxide; Disease Models, Animal; Glycine; Interleukin-8; Leukocyte Elastase; Lung Injury; Male; Oxygen; Partial Pressure; Proteinase Inhibitory Proteins, Secretory; Rats; Rats, Sprague-Dawley; Serine Proteinase Inhibitors; Sulfonamides; Tumor Necrosis Factor-alpha

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

Major burn injury induces an inflammatory response that is accompanied by the release of various cytokines. We investigated the gradual changes in the levels of pro-inflammatory and anti-inflammatory cytokines following burn injury and determined the relationship between these levels and burn size in adult Korean patients with burn injury.. Blood samples from 9 healthy controls and 60 Korean burn patients were collected on days 1, 3, 7, 14, and 21 after burn injury, and concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF) were measured. Burn patients were divided into 3 groups according to burn size (15-30%, 31-50%, >50% total body surface area), and the concentrations of the cytokines were compared between these groups and the control group over 3 weeks.. Compared to their levels in controls, IL-6, IL-8, IL-10, TNF-α, and G-CSF levels in burn patients were significantly higher during the observation period. Median concentrations of IL-8, IL-10, and G-CSF at each time point increased with burn size, although peak levels and time to peak levels of these cytokines differed from patient to patient.. These findings indicate that IL-6, IL-8, IL-10, TNF-α, and G-CSF are important mediators in inflammatory changes after burn injury; however, various factors, including burn size, may influence the concentrations of these cytokines.

Topics: Adolescent; Adult; Aged; Asian People; Burns; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Republic of Korea; Time Factors; Tumor Necrosis Factor-alpha; Young Adult

Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD.

Topics: Adolescent; Adult; Burns; Cells, Cultured; Chemokine CCL2; Child, Preschool; Cicatrix, Hypertrophic; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Flow Cytometry; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Myeloid Differentiation Factor 88; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger; Skin; Toll-Like Receptor 4; Transfection

During acute lung injury, nitric oxide (NO) exerts cytotoxic effects by reacting with superoxide radicals, yielding the reactive nitrogen species peroxynitrite (ONOO(-)). ONOO(-) exerts cytotoxic effects, among others, by nitrating/nitrosating proteins and lipids, by activating the nuclear repair enzyme poly(ADP-ribose) polymerase and inducing VEGF. Here we tested the effect of the ONOO(-) decomposition catalyst INO-4885 on the development of lung injury in chronically instrumented sheep with combined burn and smoke inhalation injury. The animals were randomized to a sham-injured group (n = 7), an injured control group [48 breaths of cotton smoke, 3rd-degree burn of 40% total body surface area (n = 7)], or an injured group treated with INO-4885 (n = 6). All sheep were mechanically ventilated and fluid-resuscitated according to the Parkland formula. The injury-related increases in the abundance of 3-nitrotyrosine, a marker of protein nitration by ONOO(-), were prevented by INO-4885, providing evidence for the neutralization of ONOO(-) action by the compound. Burn and smoke injury induced a significant drop in arterial Po(2)-to-inspired O(2) fraction ratio and significant increases in pulmonary shunt fraction, lung lymph flow, lung wet-to-dry weight ratio, and ventilatory pressures; all these changes were significantly attenuated by INO-4885 treatment. In addition, the increases in IL-8, VEGF, and poly(ADP-ribose) in lung tissue were significantly attenuated by the ONOO(-) decomposition catalyst. In conclusion, the current study suggests that ONOO(-) plays a crucial role in the pathogenesis of pulmonary microvascular hyperpermeability and pulmonary dysfunction following burn and smoke inhalation injury in sheep. Administration of an ONOO(-) decomposition catalyst may represent a potential treatment option for this injury.

Topics: Animals; Burns; Capillary Permeability; Catalysis; Disease Models, Animal; Female; Hemodynamics; Interleukin-8; Lung; Metalloporphyrins; Peroxidase; Peroxynitrous Acid; Poly(ADP-ribose) Polymerases; Pulmonary Circulation; Sheep; Smoke Inhalation Injury; Tyrosine; Vascular Endothelial Growth Factor A

The role of the Toll-like receptor 4 (TLR4), a component of the innate immune system, in the development of burn-induced acute lung injury (ALI) has not been completely defined. Recent data suggested that an intact TLR4 plays a major role in the development of organ injury in sterile inflammation. We hypothesized that burn-induced ALI is a TLR4-dependent process. Male C57BL/6J (TLR4 wild-type [WT]) and C57BL/10ScN (TLR4 knockout [KO]) mice were subjected to a 30% total body surface area steam burn. Animals were killed at 6 and 24 h after the insult. Lung specimens were harvested for histological examination after hematoxylin-eosin staining. In addition, lung myeloperoxidase (MPO) and intercellular adhesion molecule 1 immunostaining was performed. Lung MPO was measured by an enzymatic assay. Total lung keratinocyte-derived chemoattractant (IL-8) content was measured by enzyme-linked immunosorbent assay. Western blot was performed to quantify phosphorylated IκBα, phosphorylated nuclear factor κB p65 (NF-κBp65), and high mobility group box 1 expression. Acute lung injury, characterized by thickening of the alveolar-capillary membrane, hyaline membrane formation, intraalveolar hemorrhage, and neutrophil infiltration, was seen in WT but not KO animals at 24 h. Myeloperoxidase and intercellular adhesion molecule 1 immunostaining of KO animals was also similar to sham but elevated in WT animals. In addition, a reduction in MPO enzymatic activity was observed in KO mice as well as a reduction in IL-8 levels compared with their WT counterparts. Burn-induced ALI develops within 24 h after the initial thermal insult in our model. Toll-like receptor 4 KO animals were clearly protected and had a much less severe lung injury. Our data suggest that burn-induced ALI is a TLR4-dependent process.

Topics: Acute Lung Injury; Animals; Blotting, Western; Burns; Enzyme-Linked Immunosorbent Assay; High Mobility Group Proteins; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Mice; Mice, Inbred C57BL; NF-KappaB Inhibitor alpha; Peroxidase; Toll-Like Receptor 4; Transcription Factor RelA

Although the beneficial effects of inducible nitric oxide synthase (iNOS) inhibition in acute lung injury secondary to cutaneous burn and smoke inhalation were previously demonstrated, the mechanistic aspects are not completely understood. The objective of the present study is to describe the mechanism(s) underlying these favourable effects. We hypothesised that iNOS inhibition prevents formation of excessive reactive nitrogen species and attenuates the activation of poly(ADP) (poly(adenosine diphosphate)) ribose polymerase, thus mitigating the severity of acute lung injury in sheep subjected to combined burn and smoke inhalation.. Adult ewes were chronically instrumented for a 24-h study and allocated to groups: sham: not injured, not treated, n = 6; control: injured, not treated, n = 6; and BBS-2: injured treated with iNOS dimerisation inhibitor BBS-2, n = 6. Control and BBS-2 groups received 40% total body surface area 3rd-degree cutaneous burn and cotton smoke insufflation into the lungs under isoflurane anaesthesia.. Treatment with iNOS inhibitor BBS-2 significantly improved pulmonary gas exchange (partial pressure of oxygen in the blood/fraction of inspired oxygen (PaO₂/FiO₂) 409 ± 43 mmHg vs. 233 ± 50 mmHg in controls, p < 0.05) and reduced airway pressures (peak pressure 20 ± 1 cm H₂O vs. 28 ± 2 cm H₂O in controls, p < 0.05) and lung water content (lung wet-to-dry ratio 4.1 ± 0.3 vs. 5.2 ± 0.2 in controls, p < 0.05) 24h after the burn and smoke injury. BBS-2 significantly reduced the increases in lung lymph nitrite/nitrate (10 ± 3 μM vs. 26 ± 6 μM in controls, p < 0.05) and 3-nitrotyrosine (109 ± 11 (densitometry value) vs. 151 ± 18 in controls, p < 0.05). Burn/smoke-induced increases in lung tissue nitrite/nitrate, poly(ADP)ribose polymerase, nuclear factor-κB (NF-κB) activity, myeloperoxidase activity and malondialdehyde formation and interleukin (IL)-8 expression were also attenuated with BBS-2.. The results provide strong evidence that BBS-2 ameliorated acute lung injury by inhibiting the inducible nitric oxide synthase/reactive nitrogen species/poly(ADP-ribose) polymerase (iNOS/RNS/PARP) pathway.

Topics: Analysis of Variance; Animals; Burns; Disease Models, Animal; Female; Imidazoles; Immunohistochemistry; Interleukin-8; Lung; Malondialdehyde; NF-kappa B; Nitric Oxide Synthase Type II; Peroxidase; Piperazines; Pulmonary Gas Exchange; Pyrimidines; RNA, Messenger; Sheep; Smoke Inhalation Injury; Tyrosine

Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the systemic inflammatory response induced by endotoxin and improves myocardial function during ischemic shock and reperfusion.. Rats received full-thickness burn wounds to 30% total body surface area followed by delayed resuscitation. The treatment group received 50,000 U/kg of ulinastatin and the burn group was given vehicle only. A sham group was not burned but otherwise was treated identically. After killing, blood and lung samples were harvested for histology and measurement of inflammatory mediators.. Administration of ulinastatin significantly decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1β, -6, and -8 both locally and systemically in burn-injured rats. The secretion of neutrophil elastase and myeloperoxidase in the lung and the expression of intercellular adhesion molecule-1 on the surface of lung epithelium were inhibited by ulinastatin. Ulinastatin also reduced the increase in pulmonary microvascular permeability. Consistent with these findings, ulinastatin ameliorated the lung edema and pulmonary oxygenation in burn-injured rats.. These results indicate that the inhibitory effects of ulinastatin on inflammatory mediator production, neutrophil activation, and microvascular permeability are associated with the recovery of pulmonary functions in severe burn-induced acute lung injury and suggest that ulinastatin may serve as a potential therapeutic administration in critical burn care.

Topics: Acute Lung Injury; Analysis of Variance; Animals; Burns; Edema; Female; Glycoproteins; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocyte Elastase; Lung; Microcirculation; Peroxidase; Rats; Rats, Sprague-Dawley; Respiratory Function Tests; Reverse Transcriptase Polymerase Chain Reaction; Trypsin Inhibitors; Tumor Necrosis Factor-alpha

To observe the effect of intestinal trefoil factor (ITF) combined with mucin on immune function of intestinal epithelial cells (IEC) after being treated with burn rat serum.. The rat IEC-6 cell lines were divided into control group (C, cultured in DEME medium containing 10% calf serum), burn control group (BC, cultured in DEME medium containing 10% burn rat serum), burn serum + ITF group (B + I, cultured in DEME medium containing 10% burn rat serum and 25 microg/mL ITF), burn serum + mucin group (B + M, cultured in DEME medium containing 10% burn rat serum and 250 microg/mL mucin), and burn serum + ITF + mucin group (B + I + M, cultured in DEME medium containing 10% burn rat serum, 25 microg/mL ITF, and 250 microg/mL mucin) according to the random number table. Meanwhile, 200 microL suspension of E. coli with density of 1 x 10(8) CFU/mL was added to each culture. At post culture minute (PCM) 15, 30 and post culture hour (PCH) 1, 2, 3, the number of bacteria adherent to IEC-6 was counted after Wright-Giemsa staining, and cell survival rate was calculated after trypan blue staining, with 20 samples in each group at each time point. (2) Other samples of IEC-6 cells without addition of E. coli were divided into BC, B + I, B + M, and B + I + M groups with the same treatment as above. The supernatant contents of IL-6, IL-8, and TNF-alpha were determined by radioimmunoassay at PCH 3, 6, 12, 24, 48, with 6 samples in each group at each time point. Data were processed with t test.. (1) Compared with that in C group, count of adherent bacteria to IEC-6 in BC group at each time point was significantly increased (with t values from 2.947 to 8.149, P values all below 0.01). Compared with those in BC group, the counts in B + I, B + M, B + I + M groups at the major time points were significantly decreased (with t values from -4.733 to -2.180, P < 0.05 or P < 0.01). (2) Compared with that in C group, cell survival rate in BC group at each time point was obviously lowered (with t values from -4.126 to -2.363, P values all below 0.05). Cell survival rates in B + I and B + M groups at some time points were significantly elevated as compared with those in BC group (with t values from 2.120 to 3.423, P < 0.05 or P < 0.01). Cell survival rate in B + I + M group at PCM 15 and PCH 3 was respectively (96.7 +/- 2.4)% and (84.0 +/- 6.7)%, which was respectively higher than that in B + I and B + M groups [(94.5 +/- 3.1)%, t = 2.507, P < 0.05; (77.1 +/- 8.2)%, t = 2.934, P < 0.01]. (3) The contents of TNF-alpha in supernatant of B + I + M group at PCH 6, 12, 24, 48 were significantly lower than those in the other 3 groups (with t values from -6. 914 to -2.889, P < 0.05 or P < 0.01). The contents of IL-6 in supernatant of B + I + M group at some time points were significantly lower than those in the other 3 groups (with t values from -7. 657 to -2.580, P < 0.05 or P < 0.01). The contents of IL-8 in supernatant of B + I + M group at PCH 6, 12, 24, 48 were significantly lower than those in BC and B + M groups (with t values from - 8.802 to - 3.640, P values all below 0.01), and those in B + I + M group at PCH 12, 24 were lower than those in B + I group (with t value respectively -2.786, -2.740, P value all below 0.05).. ITF can maintain immune function and homeostasis of IEC, prevent bacterial adherence, decrease cell death rate, and reduce release of inflammatory mediators. The effect can be strengthened with addition of mucin.

Topics: Animals; Bacterial Adhesion; Burns; Cell Line; Epithelial Cells; Interleukin-6; Interleukin-8; Intestinal Mucosa; Intestines; Mucins; Peptides; Rats; Serum; Trefoil Factor-2; Tumor Necrosis Factor-alpha

High-mobility group box protein 1 (HMGB1) is a nuclear protein that may be released actively from monocytes and macrophages or passively from necrotic or damaged cells. Several experimental data suggest that burn injury is accompanied by elevated plasma HMGB, but there are only few data available about its changes in burned patients. The aim of this study was to follow the time course and the prognostic value of plasma HMGB1 and cytokine changes in patients with severe burn injury affecting more than 10% of body surface area (n = 26). Blood samples were taken on admission and on the following 5 days. Plasma HMGB1 concentration was measured by the enzyme-linked immunosorbent assay method, whereas IL-6, IL-8, and IL-10 were assayed by the cytometric bead array kit. The HMGB1 and IL-10 concentrations were elevated on admission and gradually decreased thereafter. Significant differences were observed between survivors and nonsurvivors in HMGB1 (P < 0.01) and IL-10 (P < 0.001) concentrations on admission with higher levels in nonsurvivors. IL-6 and IL-8 started to increase markedly from day 2. Positive correlation (r = 0.669, P < 0.01) was found between burned body surface and HMGB1 on admission. Receiver operating characteristic analysis of data on admission showed that at a level of 16 ng/mL, HMGB1 indicated lethality, with 75.0% sensitivity and 85.7% specificity. Using the cutoff level of 14 pg/mL, IL-10 predicted intensive care unit mortality, with 85.7% sensitivity and 84.2% specificity. Very early HMGB1 and IL-10 release may have an important impact on the immune function of patients after burn trauma.

Topics: Adult; Aged; Burns; Cytokines; Female; HMGB1 Protein; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Prognosis; Sepsis; Severity of Illness Index

Thermal burn injury induces inflammatory cell infiltrates in the dermis and thickening of the epidermis. Following a burn injury, various mediators, including reactive oxygen species (ROS), are produced in macrophages and neutrophils, exposing all tissues to oxidative injury. The anti-oxidant activities of flavonoids have been widely exploited to scavenge ROS. In this study, we observed that several flavonoids-kaempferol, quercetin, fisetin, and chrysin-inhibit LPS-induced IL-8 promoter activation in RAW 264.7 cells. In contrast with quercetin and fisetin, pretreatment of kaempferol and chrysin did not decrease cell viability. Inflammatory cell infiltrates in the dermis and thickening of the epidermis induced by burn injuries in mice was relieved by kaempferol treatment. However, the injury was worsened by fisetin, quercetin, and chrysin. Expression of TNF-a induced by burn injuries was decreased by kaempferol. These findings suggest the potential use of kaempferol as a therapeutic in thermal burn-induced skin injuries. [BMB reports 2010; 43(1): 46-51].

Topics: Animals; Burns; Cell Differentiation; Cell Line, Tumor; Flavonoids; Flavonols; Interleukin-8; Kaempferols; Lipopolysaccharides; Mice; Quercetin; Reactive Oxygen Species; Skin; Tumor Necrosis Factor-alpha

Increased catecholamine (CA) levels after severe burn are associated with stress, inflammation, hypermetabolism, and impaired immune function. The CA secretion profiles in burned patients are not well described. Mechanisms, duration, and extent of CA surge are unknown. The purpose of this large unicenter study was to evaluate the extent and magnitude of CA surge after severe burn in pediatric patients. Patients admitted between 1996 and 2008 were enrolled in this study. Twenty-four-hour urine collections were performed during acute hospitalization and up to 2 years postburn. Results from the samples collected from 12 normal, healthy volunteers were compared with the data from the burned patients. Relevant demographic and clinical information was obtained from medical records. Student t-test and one-way ANOVA were used to analyze the data where appropriate. Significance was accepted at P < 0.05. Four hundred thirteen patients were enrolled in this study; 17 patients died during acute hospitalization. Burn caused a marked stress and inflammatory response, indicated by massive tachycardia and elevated proinflammatory cytokines. In burned patients, CA levels are consistently and significantly modulated after burn when compared with the levels in normal, healthy volunteers. Catecholamine levels were significantly higher in boys compared with girls, correlated with burn size in burns greater than 40%, and were increased in older children. There were differences over time in survivors versus nonsurvivors, with CA levels significantly higher in nonsurvivors at two time points. Inflammatory cytokines show a similar profile during the study period. Our study gives clinicians a useful insight into the extent and magnitude of CA elevation to better design treatment strategies.

Topics: Adolescent; Age Factors; Burns; Catecholamines; Child; Child, Preschool; Cytokines; Dopamine; Epinephrine; Female; Granulocyte Colony-Stimulating Factor; Heart Rate; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Norepinephrine; Sex Factors; Tumor Necrosis Factor-alpha

To evaluate the effects of a monoclonal antibody against interleukin-8 (K2.2) on the microvascular fluid flux after combined injury by burn and smoke inhalation.. Fourteen sheep were prepared surgically by placing a lung lymph catheter and a flank lymph catheter to examine the microvascular fluid flux. After a recovery period, they were subjected to a combined injury of 40% third-degree burns on the flank and smoke inhalation.. This combined injury induced a rapid increase in burned tissue lymph flow (b-Q(L)) and a delayed-onset increase in lung lymph flow (l-Q(L)). The initial increase in b-Q(L) was associated with an elevation of the lymph-to-plasma oncotic pressure ratio, which led to a predominant increase in the burned tissue permeability index (b-PI). Pretreatment with K2.2 had no effect on the permeability change seen in the burned tissue; however, the lung permeability changes were attenuated by pretreatment with K2.2.. These findings indicate that the pathogenesis of the increase in microvascular fluid flux seen after the combined injury differs in burned tissue and the lung.

Topics: Acute Lung Injury; Animals; Antibodies, Monoclonal; Burns; Female; Hemodynamics; Hypoxia; Interleukin-8; Oxygen Consumption; Permeability; Pulmonary Circulation; Sheep; Smoke Inhalation Injury

Severe burn causes a pronounced hypermetabolic response characterized by catabolism and extensive protein wasting. We recently found that this hypermetabolic state is driven by a severe inflammatory response. We characterized in detail the kinetics of serum levels of a panel of cytokines in a rat model, which may serve as reference for the development of therapeutic interventions applicable to humans. Male Sprague-Dawley rats (n = 8) received a full-thickness burn of 60% total body surface area. Serum was harvested 1, 3, 6, 12, 24, 48, 96, and 168 h after burn. Eight serum cytokines commonly used to assess the inflammatory response in humans, such as IL-1beta, IL-6, IL-10, TNF, vascular endothelial growth factor, and monocyte chemotactic protein 1, and the rat-specific cytokines cytokine-induced neutrophil chemoattractant (CINC) 1, CINC-2, and CINC-3 were measured by enzyme-linked immunosorbent assay technique and were compared with controls (n = 4). Statistical analysis was conducted using the t test, with P < 0.05 considered as significantly different. Thermal injury resulted in significantly increased serum levels of IL-1beta, IL-6, IL-10, monocyte chemotactic protein 1, CINC-1, CINC-2, and CINC-3 when compared with the concentrations detected in nonburned rats (P < 0.05). Serum levels of TNF-alpha and vascular endothelial growth factor in burned rats were not found to be significantly different to controls. Burn causes a profound inflammatory response in rats. Specific cytokines known to increase in humans postburn such as IL-1 beta, IL-6, IL-10, MCP-1, and IL-8 (CINC-1, CINC-2, and CINC-3 in the rat) were also observed in our rat burn model, which now allows us to study new anti-inflammatory treatment options.

Topics: Animals; Burns; Chemokine CCL2; Chemokine CXCL1; Chemokines, CXC; Enzyme-Linked Immunosorbent Assay; Inflammation; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

To evaluate the effects of peritoneal lavage fluids from radiation injury, burn injury and combined radiation-burn injury on the growth of hematopoietic progenitor cells (HPC).. Rats were divided into four groups: A radiation group (RG), a burn group (BG), a combined radiation-burn group (CRBG) and normal control group (NG). RG and CRBG rats were irradiated with 12 Gy, and burns of 30% total body surface area were generated in group BG and group CRBG. Peritoneal lavage fluids were collected and tested for their effects on the growth of erythrocyte progenitor cells or granulocyte-macrophage progenitor cells of BALB/c mice in vitro.. The numbers of colony forming units-erythroid (CFU-E), burst forming units-erythroid (BFU-E) and colony-forming units-granulocyte-macrophage (CFU-GM) formed after treatment with lavage fluids from BG or CRBG were significantly higher than those from NG. However, fewer CFU-E, BFU-E or CFU-GM colonies were found after treatment with lavage fluid from the RG. In lavage fluid from BG and CRBG, the concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFalpha) was increased in comparison to NG and RG. Treatment with these cytokines had similar promoting effects on the growth of hematopoietic colonies and neutralizing antibodies inhibited these effects significantly.. Burns increase the responsiveness of the system and help the proliferation of hematipoietic progenitor cells, while radiation decreases all these responses relative to both the controls and the burn plus radiation group.

Topics: Animals; Ascitic Fluid; Burns; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytokines; Erythroid Cells; Hematopoietic Stem Cells; Interleukin-6; Interleukin-8; Mice; Mice, Inbred BALB C; Radiation Injuries, Experimental; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Whole-Body Irradiation

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

To investigate the effect of nuclear factor-kappaB (NF-kappaB) activation on the expression of proinflammatory cytokines in the lung tissues of rats with early-stage burn injury.. Wistar rats were randomly divided into 3 groups, namely the normal control, burn, burn and PDTC treatment groups, and in the latter two groups, the rats were subjected to 35% TBSA full-thickness burns. Activation of pulmonary NF-kappaB at 1, 3, 6, 12, and 24 postburn hour (PBH) was tested by electrophoretic mobility shift assay , and the expressions of pulmonary tumor necrosis factor alpha (TNF alpha) and interleukin-8 (IL-8) mRNAs at 3, 6, 12, and 24 h were detected by RT-PCR.. Compared to that of the control group, activity of pulmonary NF-kappaB in burned rats was markedly increased within 1 PBH and kept increasing till 24 h. Expressions of pulmonary TNF alpha and IL-8 mRNAs increased gradually, reaching the peak level at 6 PBH, and PDTC could effectively inhibit pulmonary NF-kappaB activation and expression of the pulmonary cytokines induced by the burn injury.. Severe burn injury may activate pulmonary NF-kappaB, which ultimately leads to secretion of cytokines in the lung tissues.

Topics: Animals; Burns; Disease Models, Animal; Gene Expression; Humans; Inflammation Mediators; Interleukin-8; Lung; NF-kappa B; Random Allocation; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

To investigate the influence of early tangential excision within 24 postburn hours on local wound inflammatory response and tissue injury in patients with deep partial thickness burn.. Twelve patients with deep partial thickness burn were enrolled in the study. Tangential excision was performed within 24 postburn hours. The same wound of a patient was divided into three areas for harvesting tissue samples, i.e. pre-operation, post-operation and non-operation areas. For each patient, the biopsies from the pre-operation area were harvested before tangential excision, while those from post-operation and non-operation areas were harvested during 5 to 7 postburn days (PBDs). The contents of IL-8, MPO and MDA in wound tissue were determined by tissue culture and chemical colorimetry, respectively. HE and Mason's staining were employed to assess the degree of necrosis of the wound tissue.. The IL-8, MPO and MDA contents in the local wound tissue after tangential excision were 6.83 +/- 1.85 microg/L, 4.07 +/- 0.87 U/g, and 8.94 +/- 5.66 micromol/g, respectively, which were significantly lower than those from non-operation area (P < 0.01). The inflammatory response in the non-operative wound area was distinct with expansion of necrotic tissue area. In contrast, the local inflammatory response of the wound after tangential excision was ameliorated without the enlargement of necrotic tissue area.. Tangential excision within 24 postburn hours could be beneficial in ameliorating local inflammatory response, and in preventing progressive deepening of the burn wounds, thus it could accelerate wound healing in patients with deep partial thickness burn.

Topics: Adult; Burns; Female; Humans; Inflammation; Interleukin-8; Male; Malondialdehyde; Middle Aged; Peroxidase; Surgical Wound Infection; Wound Healing

Acute lung injury is a common complication in patients with extensive burns in which the burned area exceeds 30% of the total body surface area (TBSA). This study was undertaken to evaluate the effect of Ligustrazine on burn-induced lung injury as well as the release of interleukin-8 (IL-8) in rats to characterize the role of Ligustrazine and IL-8 in lung injury after burn trauma. Sprague-dawley rats were divided into three groups: (1) sham group, rats who underwent sham burn; (2) control group, rats given third-degree burns over 30% TBSA and lactated Ringer solution for resuscitation; and (3) Ligustrazine group, rats given burn injury and lactated Ringer's solution with Ligustrazine inside for resuscitation. Pulmonary injury was assessed at 24 h by pulmonary capillary permeability determined with fluorescein isothiocyanate-labeled albumin and lung histologic analysis, and lung myeloperoxidase (MPO) activity as well as lung wet/dry weight ratio. The IL-8 levels were measured in serum by enzyme-linked immunosorbent assay. These studies showed that burn trauma results in increased pulmonary leakage permeability and lung wet/dry ratio, elevated serum IL-8 levels and MPO activity, and worsened histologic condition. Ligustrazine inhibited these changes, prevented burn-mediated lung injury, and the production of IL-8. This will likely provide further evidence for ligustrazine as a therapeutic strategy in burn-induced lung injury.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Burns; Capillary Permeability; Interleukin-8; Lung; Male; Models, Animal; Peroxidase; Pyrazines; Random Allocation; Rats; Rats, Wistar; Respiratory Distress Syndrome

To study the dynamic changes in the lymphokines and the changes in tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8) levels in the lymph during shock stage of rats with major burns.. Forty-two male adult Wistar rats were randomly divided into burn resuscitation group (A, n = 18), burn non-resuscitation (B, n = 18) and the control (C, n = 6) groups. The TNF-alpha, IL-6 and IL-8 levels in the lymph were determined with radioimmunoassay at 6, 24, 48 postburn hours (PBH). The lymphokines in the mesenteric lymphatic vessels was observed at 6, 24 and 48 PBH with inverted microscopy and digital image processing, and the contraction frequency of the lymphatic was calculated. The lymph was collected by cannulation of the chylous cistern, and its speed of flow was calculated.. The lymphatic contents of TNF-alpha and IL-6 in both A and B groups began to increase at 6PBH, reaching the peak values at 24 PBH (TNF-alpha in A and B groups were 1.61 +/- 0.27 ug/L and 1.86 +/- 0.34 ug/L, respectively; IL-6 in A and B groups were 398 +/- 67 ng/L and 572 +/- 97 ng/L, respectively), and they were significantly higher than those in C group at each time points (P < 0.01), meanwhile there was also obvious difference in them between A and B groups (P < 0.01). The lymphatic contents of IL-8 in A and B groups began to increase at 24 PBH, and continued to increase till 48PBH (540.29 +/- 0.32 ng/L in A group, 863.48 +/- 105.16 ng/L in B group), which were evidently higher than those in C group (P < 0.01). There was significant difference in IL-8 contents between A and B groups (P < 0.01). The contraction frequency of the mesenteric lymphatic vessels in A and B groups were decreased, especially so at 24 PBH (P < 0.01). The speed of lymphatic flow in A and B groups was increased at each time points (P < 0.01). The central chylous vessels in the villi of the small intestine were extremely dilated as seen under microscope.. After burn injury, the lymphatic vessels dilated, with its motility decreased and speed of flow increased, and the contents of TNF-alpha, IL-6 and IL-8 in lymph were increased during the shock stage of burn rats. Fluid resuscitation could improve the lymph circulation.

Topics: Animals; Burns; Disease Models, Animal; Interleukin-6; Interleukin-8; Lymph; Male; Rats; Rats, Wistar; Shock, Traumatic; Tumor Necrosis Factor-alpha

To explore the microvessel counts and the expressions of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 ( MIP-1) alpha mRNA in the pathological scar tissues.. Immunohistochemical method of avidin-biotin complex was used for microvessel counts on the routinely formalin-fixed and paraffin-embedded sections of specimens of hypertrophic scars, keloids, normal skin, and surgical scar, and in situ hybridization for the expressions of IL-8, MCP-1, MIP-1alpha mRNA.. The microvessel counts as well as the positive rates and the scorings of IL-8, MCP-1, and MIP-1alpha mRNA were significantly higher in pathological scars than those in the normal skin and surgical scar (all P < 0.05). The microvessel counts were significantly higher in the positive cases of IL-8, MCP-1 and MIP-1alpha mRNA than those in the negative ones (P < 0.05). The close positive correlations were found among the microvessel counts and the expressive scorings of 3 factors (P < 0.05). The close positive correlations were also found among the expressive scorings of IL-8, MCP-1, and MIP-1alpha mRNA in pathological scars. Microvessel counts were significantly higher in hypertrophic scars with the course less than 1 year than those with the course more than 1 year.. IL-8, MCP-1 and MIP-1alpha play important roles in promoting the neovascularization of pathological scars.

Topics: Adolescent; Adult; Burns; Capillaries; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Cicatrix; Female; Humans; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; RNA, Messenger; Skin

Pulmonary dysfunction after smoke inhalation and thermal injury is associated with excessive morbidity and mortality. The purpose of this study was to evaluate alveolar leukocyte function after thermal injury and smoke inhalation.. Twenty-one patients with thermal injury only (n = 8); thermal injury and smoke inhalation injury (n = 8); and nonburned controls (n = 5) were assessed by means of bronchoscopically directed lavage (bronchoalveolar lavage [BAL]) on the first and fourth days postinjury. BAL-isolated pulmonary leukocytes were assessed for number, composition, viability, and production of tumor necrosis factor (TNF)alpha, interleukin (IL)-8, and IL-6 in response to 100 ng/mL of lipopolysaccharide (LPS) (mean +/- SEM; significance at p < 0.05).. Six of eight Smoke patients had gross evidence of lung injury. On day 1, Smoke and Burn BAL isolates yielded greater cell counts than Control (10.6 vs. 4.5 vs. 2.4 x 10(6)/mL). Smoke macrophages on day 1 produced more TNFalpha (1.2 vs. 0.2 ng/mL), IL-6 (8.0 vs. 1.9 ng/mL), and IL-8 (85 vs. 32 ng/mL) after LPS stimulation compared with respective unstimulated (0 ng/mL of LPS) day-1 Smoke cells. LPS-stimulated Burn cells on day 1 produced more IL-8 (150 vs. 62 ng/mL) but not TNFalpha (0.4 vs. 0.25 ng/mL) or IL-6 (1.8 vs. 0.69 ng/mL), when compared with respective unstimulated Burn cells. By day 4, LPS-stimulated Smoke and Burn cells produced significantly more TNFalpha (Smoke, 0.41 vs. 0.16 ng/mL; Burn, 0.87 vs. 0.51 ng/mL) and IL-6 (Smoke, 2.5 vs. 0.47 ng/mL; Burn, 4.1 vs. 1.47 ng/mL), but not IL-8 (Smoke, 51.1 vs. 51.1 ng/mL; Burn, 54.4 vs. 55.6 ng/mL), compared with respective unstimulated day-4 cells.. Smoke inhalation induces a massive influx of alveolar leukocytes that are primed for an early, enhanced LPS-activated cytokine response compared with alveolar leukocytes isolated after burn injury alone or normal controls.

Topics: Adult; Analysis of Variance; Bronchoalveolar Lavage; Bronchoscopy; Burns; Female; Humans; Interleukin-6; Interleukin-8; Leukocytes; Lipopolysaccharides; Macrophages, Alveolar; Male; Smoke Inhalation Injury; Tumor Necrosis Factor-alpha

To investigate the effects of NF-kappaB activation on the expression of cytokines in monocytes stimulated by burn serum, so as to explore the mechanism in monocyte activation by burn serum.. Peripheral blood monocytes (PBMCs) isolated from healthy volunteers were employed as the target cells. The cells were stimulated by serum from healthy volunteers (control), by serum from burn patients (burn serum), and by burn serum with addition of PDTC (pyrrolidine dithiocarbamate). Activation of monocytic NF-kappaB before stimulation and at 0.5, 1.0, 2.0 and 4.0 poststimulation hours (PSH) was assessed with electrophoretic mobility shift assay (EMSA). Expression of TNF-alpha and IL-8 mRNA at 1.0, 2.0, 4.0, 6.0 PSHs was assayed with in situ hybridization (ISH). Meanwhile, the contents of TNF-alpha and IL-8 in the supernatants were assayed by enzyme linked immunosorbent assay (ELISA).. The monocytic NF-kappaB activity in burn serum group increased significantly and reached the peak level at 1 PSH [(30.2 +/- 3.5) x 10(4) integration gray scale value] after the PBMCs were stimulated by burn serum, and it was obviously higher than that in control group [(4.4 +/- 0.8) x 10(4) integration gray scale value], (P < 0.01). It gradually decreased and returned to the pre-stimulation state at 2 PSH. The monocytic NF-kappaB activity in PDTC group decreased to [(6.8 +/- 0.9) x 10(4) integration gray scale value at 1 PSH] after the stimulation. The expression of TNF-alpha mRNA of the monocytes and the TNF-alpha level in the supernatant of the cultured PBMCs reached peak level at 1 PSHs after being stimulated by burn serum, and they were obviously higher than those in control group (P < 0.01). While the expression of IL-8 mRNA and the IL-8 level in the supernatant of the cultured PBMCs reached peak level at the 4 PSHs after being stimulated by burn serum, which were obviously higher than those in control group (P < 0.01) too. In addition, the synthesis and release of TNF-alpha (peaked at 1 PSH: 0.52 +/- 0.06 microg/L) and IL-8 (peaked at 4 PSH: 239 +/- 20 ng/L) in the supernatant of PBMCs in PDTC group were evidently higher than those in control group [(0.13 +/- 0.07) microg/L, < 156 ng/L] (P < 0.01).. Burn serum can induce the activation of NF-kappaB which lead to the synthesis and release of cytokines from PBMC. This result indicates that the activation of NF-kappaB plays important role in the secretion of cytokines from PBMCs induced by the burn serum.

Topics: Adolescent; Adult; Burns; Female; Humans; In Vitro Techniques; Interleukin-8; Male; Middle Aged; Monocytes; NF-kappa B; Serum; Signal Transduction; Tumor Necrosis Factor-alpha

Cytokines have been considered as important participants in the post-burn pathophysiological process. The aim of this study was to investigate the course of a proinflammatory cytokine interleukin-8 (IL-8) and an anti-inflammatory cytokine IL-10 in burned patients and whether there was a correlation between mortality and serum levels of these cytokines. Thirty-six acutely burned patients, admitted to Ankara Numune hospital burn unit, entered into the study. A series of serum samples were collected, and serum levels of IL-8 and IL-10 were determined using enzyme-linked immunosorbent assay kit. According to definition utilised, 21 patients developed septic shock and nine of them died. There was no mortality among the 17 non-septic patients. In all 36 patients, there was an increase in serum IL-8 levels, and a peak level was detected shortly after burn injury. The peak IL-8 value of the non-survivors was greater when compared with that of the others. On admission, a significant difference in serum IL-8 values was found between survivors and those who died. In all patients, a peak level of IL-10 was detected between 5 and 9 days of injury. In non-septic survivors, this peak level was less when compared with that of the others. After this peak level, in all patients, serum IL-10 levels showed a decrease, but in non-survivors, a second peak level was detected. A greater understanding of the pathology of the burn sepsis allows rationale use and assessment of current therapies. The results obtained in this study provide useful information on the formulation approaches to this task. Also, IL-8 and IL-10 are prognostic factors in burn sepsis.

Topics: Adult; Burns; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Prognosis; Sepsis

To investigate the effect of early escharectomy on resting energy expenditure (REE) in severely burned patients dynamically with the metabolic monitoring and diagnostic system.. Fifty-six adult male patients with severe burns were divided into early escharectomy (group A, n = 39, escharectomy within 5 PBDs) and non-early escharectomy (group B, n = 17, escharectomy after 5 PBDs) groups. The wounds of full thickness and deep partial thickness burn in the two groups were all excised and covered with allogeneic skin and autologous micro-skin in the first operation. The changes in REE were observed dynamically at the bedside of the patients with the metabolic monitoring and diagnostic system. The plasma contents of IL-6, IL-8, TNF-alpha and LPS from 9 patients in group A and 7 in group B were also determined dynamically.. All patients survived. The REE in both groups was elevated markedly, but REE in group A was lower compared with group B before and after escharectomy within 14 days. (P < 0.05). The plasma level of IL-6, IL-8, TNF-alpha and LPS in group A were obviously lower than those in group B (P < 0.05).. The hypermetabolic response of burn patients with severe burns could be lowered by early escharectomy, and it seemed to be related to the decrease of the release of proinflammatory mediators.

Topics: Adult; Basal Metabolism; Burns; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Postoperative Care; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

To investigate the change of the erythrocyte chemokine receptor(ECKR) binding activity in the shock stage of burn rats.. SD rats were randomly divided into two group, burn and control groups. In the burn group rats, 30% total body surface area (TBSA)were scalded to III degree. The binding activity of rat ECKR in the shock stage was detected by ELISA using IL-8 as ligand at various time points (0.5, 2, 4, 8, 16, 24 and 48 hours) after burn.. Compared with control group, the binding activity of rat ECKR declined significantly half an hour after burn and maintained at low level for 48 hours (P<0.01). The comparison of the binding activity of rat ECKR at various time points after burn indicated that the binding activity declined gradually from 2 hours (P<0.01-0.05), reached lowest value 24 hrs, and then rose significantly 48 hrs after burn (P<0.01).. The ECKR binding activity declined significantly after burn, suggesting erythrocytes may participate in the regulation of chemokines and play some role in the inflammation.

Topics: Animals; Burns; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Female; Interleukin-8; Rats; Rats, Sprague-Dawley; Receptors, Chemokine; Shock, Traumatic; Time Factors

To investigate the regulatory effect of Chinese traditional medicine mixture (CTMM) on inflammatory response in rats with severe burn.. One hundred and ten rats were randomly divided into 3 groups:scalded rats inflicted by 30% III degree scald were treated with CTMM and SD-Ag (CTMM group), scalded rats inflicted by 30% III degree scald were treated with SD-Ag alone (scalded group), and healthy rats were treated with SD-Ag (normal group). The serum contents of TNF-alpha, IL-beta, IL-6, IL-8, IL-4, and IL-10 in rats in the 3 groups were dynamically monitored.. The serum contents of TNF-alpha, IL-1beta, IL-6, IL-8, IL4, and IL-10 evidently increased in both the CTMM and scalded groups. But the contents of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, and IL-8) in the CTMM group were much lower than those in the scalded group. However, the contents of anti-inflammatory cytokines (IL-4 and IL-10) in the CTMM group were much higher than those in the scalded group.. CTMM has double-way regulatory effect on the inflammatory response in rats with severe burn.

Topics: Animals; Burns; Drug Combinations; Drugs, Chinese Herbal; Female; Interleukin-1; Interleukin-6; Interleukin-8; Male; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

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

To evaluate the influence of necrotic tissue on progressive injury in deep partial thickness burn wounds.. Tissue specimens were cultured both for estimation of IL-8, EGF, bFGF, PDGF-AB and histopathological examination, from the pre-operation, post-operation, and non-operation wounds from seven patients with deep partial thickness burn.. In seven specimens from the non-operation group, IL-8 release increased compared with those in the post-operation group (P < 0.001), while the levels of EGF, bFGF, PDGF-AB release were lower than those in the post-operation group. Histopathological examination revealed that in the non-operation group, the degree of neutrophil infiltration was enhanced, the extent of tissue necrosis enlarged, and residual skin appendages disappeared. In contrast, in the post-operation group, the degree of inflammatory response was decreased, with the formation of fresh granulation tissue and epithelialization.. This study suggests that the presence of necrotic tissue could be the inhibitory factor in the wound healing process, as it might cause tissue progressive injury leading to the delay of wound healing. To promote wound healing, active tangential excision is recommended to remove necrotic tissue.

Topics: Adult; Burns; Humans; Interleukin-8; Necrosis; Skin; Wound Healing

To investigate the prevention and treatment effects of early and short -- term use of antibiotics with broad spectrum on postburn severe infection in severely burned patients.. Thirty -- five burn patients with TBSA from 50% to 95% were enrolled in the study. The patients were divided into early prevention [20 cases, antibiotics were used started from 6 postburn hours (PBH)] and delayed prevention (15 cases, antibiotics were applied after 48 PBH) groups. Plasma levels of LPS, TNFa and IL -- 8 were dynamically monitored with the concomitant observation of clinical signs of postburn sepsis.. After major burns, the plasma levels of LPS, TNFalpha and IL -- 8 increased evidently and reached the peak values on 3 similar 5 postburn days (PBD). But the levels of all above factors in the early group were obviously lower than those in the delayed group (P < 0.05 similar 0.01). The incidencies of sepsis and internal organ complications within 2 postburn weeks were much lower in the early group than those in the delayed group (P < 0.05). The subeschar bacterial quantification on 4 similar 7 PBD was evidently lower in the early group than that in the delayed group (P < 0.01).. Early and short -- term use of antibiotics with broad spectrum in severely burned patients could effectively prevent postburn severe infection and lower down the incidence of internal organ complications.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteria; Burns; Humans; Interleukin-8; Lipopolysaccharides; Middle Aged; Sepsis; Time Factors; Tumor Necrosis Factor-alpha

To explore the effects of extensive excision of massive invasive infected burn wound on the REE of burn patients with sepsis.. REEs and plasma levels of IL -- 6, IL -- 8, TNFalpha and LPS were determined before and after surgical interventions and when patients', condition improved in 8 burned cases with sepsis.. All the 8 patients survived after treatment. The REE level in patients after operation was significantly lower than those before the operation (P < 0.01). REE in patients whose condition improved decreased obviously when compared to that after operation (P < 0.01). The plasma levels of IL -- 6, IL -- 8, TNFalpha and LPS decreased markedly after the operation when compared to those before operation (P < 0.05). and there were lower levels of these factors when the patients', condition improved (P < 0.001). Furthermore, there were closely positive correlations between REE and plasma IL -- 6, IL -- 8, TNFalpha and LPS (P < 0.01).. Over -- releasing of some inflammatory mediators could be corrected by means of extensive excision of massive invasively infected burn wound. This might be beneficial to the control or the amelioration of the hypermetabolism in burn patients with sepsis.

Topics: Adolescent; Adult; Basal Metabolism; Burns; Child; Female; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Sepsis; Time Factors; Tumor Necrosis Factor-alpha

To explore the influence of stress inhibition on the plasma levels of LPS pro-inflammatory and Th1/Th2 cytokines in severely scalded rats.. Sprague-Dawley (SD) rats inflicted by 30% TBSA of deep partial thickness burn were employed as the model and randomly divided into burn with immediate resuscitation (A) and burn with immediate resuscitation and soluble cocktail (B) groups. Plasma was harvested from peripheral blood at different postburn time points for the determination of the levels of LPS, IL-1alpha, IL-6, TNFalpha, IL-8, IL-2, IFN-gamma, IL-4 and IL-10 in the rats of the two groups. And the rats inflicted by sham scalding were taken as control group (C).. The postburn plasma levels of LPS, IL-1alpha, IL-4 and IL-10 increased gradually, while the plasma levels of IL-6, TNF, IL-8, IL-2 and IFN increased initially and decreased thereafter. The increasing ranges of LPS and these inflammatory cytokines were higher in A group, in which the increases of IL-1alpha, IL-6 and IL-4 appeared earlier in A (6 PBH) than those in B (12 PBH) groups.. Prompt fluid resuscitation and stress inhibition could delay and ameliorate the postburn inflammatory reaction, decrease the production of Th2 cytokine and partially restore the production of Th1 cytokine after 48 PBH.

Topics: Animals; Burns; Cytokines; Female; Fluid Therapy; Interferon-gamma; Interleukin-1; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Rats; Rats, Sprague-Dawley; Stress, Physiological; Th1 Cells; Time Factors; Tumor Necrosis Factor-alpha

In order to understand the role of an anti-inflammatory cytokine interleukin 10 (IL-10) in the pathophysiology of burn injury, IL-10 levels in serial serum samples of 22 burned patients were analyzed. The total body surface areas (TBSA) of the burn injury ranged from 30 to 90%. Among these 22 patients, 14 recovered and the other eight, who were septic, expired. A significant difference in serum IL-10 values on admission (5-20 h postburn) was found (P<0.05) between patients who survived or died from burn injury as analyzed by the Student's t test. In addition, a significant difference in serum IL-10 on admission was also found (P<0.05) between patients with TBSA of greater or less than 50%. An initial peak serum IL-10 response was detected within 2.5 days postburn. Significant differences in the peak serum IL-10 levels were not found between patients with TBSA of greater or less than 50% and patients who survived or expired from burn injury. Afterwards, serum IL-10 remained low in the survivors, while an increase in serum IL-10 could be detected in the non-survivors with proven sepsis. Levels of circulating IL-6 in these non-surviving patients showed a tendency to increase starting from about 1-2 weeks postburn which coincided temporally with the detection of infections. However, marked increases in circulating IL-10 levels were observed just before death in four of the eight non-survivors. The serum samples of these four patients were collected at 31 h (404.8 pg/ml), 2 h (773.9 pg/ml), 5 days (150.7 pg/ml) and 12 h (177.1 pg/ml) before the expiration of these patients, respectively. IL-10 levels of 28.6, 27. 5 and 13.5 pg/ml were detected in sera of three of the remaining four non-survivors that were collected at 2.5 h, 36 h and 30 h before the expiration of these patients, respectively. There was one non-surviving patient who suffered an 80% burn (patient D4 in Table 1 and Fig. 4) and his IL-10 level at 20 days postburn was 13.4 pg/ml. The serum sample of this patient was collected 22 days before death and he was not suffering from sepsis at this stage. In conclusion, an initial increase in serum levels of IL-10 was detected postburn. A marked increase in serum levels of IL-10 was detected in four of the eight septic patients just before their death. It was considered that a lack and/or a delay in the increase of circulating IL-10 may play a significant role in the pathophysiology of sepsis in burned patients.

Topics: Adolescent; Adult; Aged; Body Surface Area; Burns; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Patient Admission; Sepsis; Statistics as Topic; Survival Rate; Tumor Necrosis Factor-alpha

IL-18 levels in the blood of 13 sepsis patients were assessed. The IL-18 values were significantly correlated with their Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and they were a good reflection of the severity of the disease. There was also a strong correlation between the IL-18 values and the patients' inflammatory cytokine levels. The results suggested strong involvement of IL-18 in the pathogenesis of sepsis.

Topics: APACHE; Burns; Female; Humans; Interleukin-18; Interleukin-6; Interleukin-8; Male; Sepsis; Time Factors; Tumor Necrosis Factor-alpha

To investigate the clinical characteristics of invasive burn wound infection with sepsis in patients with major burns and to summarize the successful experiences in the treatment of such patients.. Eight patients with major burns, complicated by invasive burn would infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. Among them, 6 patients developed multiple organ dysfunction syndrome (MODS) and 2 developed septic shock. The plasma concentrations of IL-6, IL-8, TNF alpha and lypopolysaccharide (LPS) were assayed before and after surgical intervention, as well as when the patient's vital signs became stable.. The patients' conditions usually deteriorated abruptly when extensive invasive burn wound infection emerged. While multi-microbial infection was usually found, Pseudomonas aeruginosa was the predominant bacteria isolated from the subeschar tissue. The plasma concentrations of IL-6, IL-8, TNF alpha and LPS before surgical intervention were significantly higher than those after surgical intervention (P < 0.05). The lowest levels of the inflammatory mediators were observed when the patients' conditions became stable, and the values were significantly lower than those before surgical intervention (P < 0.001).. Since the main cause of burn wound sepsis is the presence of a large area of infected burn wound, they should be excised and covered as early as possible. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn sepsis. Although favorable results should be attributed to comprehensive treatment, we believe that early, aggressive and thorough surgical excision of infected burn wounds, followed by sound and complete coverage of the area, play a crucial role.

Topics: Adolescent; Adult; Burns; Child; Escherichia coli; Female; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Pseudomonas aeruginosa; Sepsis; Skin Transplantation; Staphylococcus aureus; Tumor Necrosis Factor-alpha; Wound Infection

Interleukin 6 (IL-6) levels in serial serum samples of 10 burned patients were analyzed. The total body surface areas (TBSA) of the burn injury varied from 30 to 85%. Among these 10 patients, five recovered and the other five, who were septic, expired. A significant difference in serum IL-6 values on admission (5-13 h postburn) was found (p < 0.05) between patients who survived or died from burn injury as analyzed by the Wilcoxon's rank sum test. In addition, a significant difference in serum IL-6 on admission was also found (p < 0.05) between patients with TBSA of greater or less than 50%. Afterwards, an initial peak serum IL-6 response was detected within 4 days postburn. Significant differences in the peak serum IL-6 levels were not found between patients with TBSA of greater or less than 50% and patients who survived or expired from burn injury. In the survivors, serum IL-6 remained low, while IL-6 increased markedly starting at about one to two weeks postburn in four of the five nonsurvivors with proven sepsis. Except for the patient who expired 42 days postburn, the maximum serum IL-6 values of the other four nonsurvivors were all greater than those of the five survivors from burn injury. Significant correlation (p < 0.05) relating the change in serum IL-6 and body temperature was observed in only two (one survivor and one nonsurvivor) of the ten patients. Changes in serum IL-6 were also compared with changes in circulating TNF-alpha and IL-8 determined previously. A similar pattern in the dynamic changes of circulating TNF-alpha, IL-8 and IL-6 was observed in the individual burned patient. An increase in serum levels of all three cytokines was detected postburn. Serum levels of three cytokines were significantly higher in the septic patients, who all died. It was considered that all three cytokines analyzed may play a significant role in the pathophysiology of sepsis in burned patients.

Topics: Adolescent; Adult; Aged; Biomarkers; Body Temperature; Burns; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis; Trauma Severity Indices; Tumor Necrosis Factor-alpha

The present study was conducted to determine whether local production of neutrophil chemoattractant cytokines preceded the influx of neutrophils following dermal scald injury. To accomplish this, dermal tissue was examined for inflammatory infiltrate and the level of KC, a murine homolog of human interleukin-8, at various time points after scald injury. The studies reveal that there was a largely neutrophilic infiltrate at 1 day post-injury which persisted for 4 days. Dermal KC levels increased significantly at 4 h, returned to baseline at 8 h and were elevated again from 1 to 3 days post-burn (P < 0.01). At 3 days post-burn, KC was elevated 15-fold above the level in sham treated mice (P < 0.01). These observations demonstrate that the influx of neutrophils into the skin follows the expression of KC in the skin. This suggests that it should be possible to alter neutrophil accumulation at the wound site by manipulating the local chemokine signal.

Topics: Animals; Burns; Chemokine CXCL1; Chemokines; Chemokines, CXC; Cytokines; Inflammation Mediators; Interleukin-8; Male; Mice; Neutrophils; Peroxidase; Skin

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

To appraise the effect of certain pro-inflammatory mediators on the pathogenesis of acute gastric mucosal lesion in early burn stage.. 21 patients with burn injuries of over 30% TBSA were divided into A and B groups according to the main clinical indexes during shock resuscitation and hemodynamic parameters. Fiberoptic endoscopic examination, determination of intramucosal pH (pHi) and measurement of some mediators were done immediately after admission to the hospital and 4 and 7 days after burn injury.. It was demonstrated that the level of LPS in plasma, the content of TNF-alpha, IL-8 and ET in group B at 4 and 7 days postburn were significantly higher than those of group A, while the value of pHi in group B was markedly lower than that of group A. Damaging index of gastric mucosa was negatively correlated with pHi (r = -0.89, P < 0.05), but positively with ET (r = 0.91, P = 0.05).. These findings suggest that the inflammatory mediators and cytokines promoted secondary damage to gastric mucosa during early postburn. It was believed that pHi was a sensitive index, and it played an important role in the development of stress ulceration.

Topics: Adolescent; Adult; Burns; Endothelins; Female; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Interleukin-8; Male; Middle Aged; Stomach Ulcer; Tumor Necrosis Factor-alpha

The aim of this study is to investigate the effect of tangential excision on the local IL-8 release and wound inflammatory response.. The tissue specimens, which were taken from 7 patients with deep partial thickness burn before and after operation, were both cultured and histopathologically examined. The level of IL-8 in the culture medium was assayed, meanwhile local inflammatory response of tissue samples was evaluated.. The result showed that the level of IL-8 is much lower in the postoperation wounds, while in the non-operation wounds the neutrophil infiltration was marked, with enlargement in necrotic area and disappearance of skin appendages.. The findings suggested that tangential excision could reduce the local production of IL-8 and decrease local inflammatory response, which is helpful to prevent the progressive necrosis of burn wound.

Topics: Adult; Burns; Culture Techniques; Female; Humans; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Postoperative Period; Wound Infection

The accumulation of sCD14 shed from human monocytes in vivo might correlate with other inflammatory parameters and could be of importance in overcoming a sepsis situation. The development of the sCD14 titer in the supernatant of monocyte-enriched MNC cultures isolated from healthy volunteers was studied utilizing a commercially available sCD14 ELISA. These culture experiments revealed the prolonged liberation of sCD14 into the supernatant during a period of several days. A medium-exchange schedule of 2-3 days was found to be superior to a longer incubation period with respect to the sCD14 yield. PMA initially enhanced the CD14 shedding slightly, but after a few hours it strongly repressed the process. Such a reduction was also achieved by protein synthesis inhibitors (cycloheximide, actinomycin D). Additionally, we monitored the concentration of sCD14, CRP, IL-6 and IL-8 in human sera from healthy persons or patients suffering from severe burn injuries with or without sepsis. Our results indicate that sCD14 is strongly correlated with IL-6, but not with IL-8. sCD14 titers were higher in the group of patients with both burn injuries and sepsis. From experiments with monocyte-enriched MNC cultures isolated from healthy volunteers and medium supplemented with sera containing sCD14 as well as radiolabeled LPS, we conclude that the enhanced shedding of CD14 in vivo during sepsis is probably not able to reduce the binding of LPS to monocytes.

Topics: Binding, Competitive; Burns; C-Reactive Protein; Cell Adhesion; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Monocytes; Protein Binding; Solubility; Tetradecanoylphorbol Acetate

The present study was conducted to determine whether a plasma interleukin-1 receptor antagonist (IL-1ra) would reflect the severity of burn injury and to examine the relation between IL-1ra and the cytokines. We studied 24 burn patients in whom the total burn surface area (TBSA) accounted for at least 20% of the body surface, and in whom serial blood samples could be obtained beginning immediately after the burn injury. Plasma levels of IL-1ra were determined by enzyme-linked immunosorbent assay (ELISA). Plasma levels of tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 were also determined by ELISA. Endotoxin was measured by an endotoxin-specific synthetic substrate method. There was a significant correlation between the plasma levels of IL-1ra and TBSA during the first week following burn injury. The IL-1ra level was the highest immediately after the burn injury. The level decreased markedly thereafter, and again rose when infection occurred. The IL-1ra level was extraordinarily elevated in patients who developed concomitant sepsis, septic shock or the septic multiple organ dysfunction syndrome. The IL-1ra level on admission and the maximum IL-1ra level during the observation period were significantly higher in the patients who eventually died than in the survivors. There was a significant correlation between the level of IL-1ra and that of TNF-alpha, IL-6 or IL-8 during the observation period. No correlation was found between IL-1ra and endotoxin. The plasma IL-1ra level was closely correlated with the severity of inflammation and the clinical status of the burn patients, regardless of the infection. Results suggest that IL-1ra can serve as an index of the systemic inflammatory response syndrome (SIRS).

Topics: Adult; Aged; Burns; Endotoxins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Interleukin-8; Male; Middle Aged; Receptors, Interleukin; Sepsis; Sialoglycoproteins; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma.. Retrospective study.. Teaching hospitals, USA and Germany.. Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points.. Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10).. Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns.. High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma.. Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.

Topics: Adolescent; Adult; Apolipoproteins; Burns; Chemokine CXCL5; Chemokines; Chemokines, CXC; E-Selectin; Female; Humans; Interleukin-8; Kinetics; Male; Multiple Trauma; P-Selectin; Retrospective Studies; Selectins; Serum Amyloid A Protein

Blood levels of various cytokines were determined in patients with burn injury immediately after the accident, and the relationship between cytokines and morbid condition was investigated. There was almost no marked elevation of cytokines in the early stage of burn injury. Throughout the entire course, tumour necrosis factor alpha, interleukin 6 and interleukin 8, as cytokines, showed high levels in patients with burn injury associated with sepsis and those who died. These levels well reflected the severity in the phase complicated with sepsis.

Topics: Accidents; Adult; Aged; Body Surface Area; Body Temperature; Burns; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Middle Aged; Prognosis; Sepsis; Survival Rate; Tumor Necrosis Factor-alpha; Wound Infection

Large burns are followed by significant trauma-induced immunomodulation, and activated neutrophils can be demonstrated in the circulation of burn patients shortly after injury. Interleukin-8 (IL-8) is a recently described molecule with neutrophil activating properties and in the present study we have measured the concentration of this cytokine in plasma from 27 patients with large burns during hospitalization using an enzyme linked immunosorbent assay (ELISA). The mean patient plasma concentration of IL-8 at admission was about 60 times higher than that of healthy controls. Furthermore, patients with total body surface area burn of more than 40% had significantly higher IL-8 concentrations in plasma than patients with smaller burns. For patients without serious infectious complications, the IL-8 concentration fell gradually after injury, whereas in patients with complicating sepsis a second peak of IL-8 was demonstrated. Thus, the increased IL-8 concentrations seem to be related to burn size and to have a role in the pathophysiology of sepsis in patients with large burns. The large amounts of circulating IL-8 following thermal injury may contribute to the strong and sustained activation of neutrophils reported earlier in patients with large burns.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Surface Area; Burns; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophil Activation; Sepsis; Trauma Severity Indices

The presence and concentration of selected cytokines (interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated in the sera of 12 burned patients (6-90 per cent body surface area). The presence of cytokines in the sera of 20 healthy volunteers (control group) was always undetectable (< 2 pg/ml). In sera of the burned patients the concentrations of IL-4 or GM-CSF were also below the test sensitivity levels, while G-CSF and IL-6 were present throughout all the observation period and IL-8 was detectable at the onset of massive infections. The serum concentrations of G-CSF and IL-6 increased during the episodes of clinically and bacteriologically detectable infections. Their increases were, however, observable 12-24 h later than the other infection symptoms. Similar increases in G-CSF and IL-6 levels have been detected during corrective surgery (covering of granulation tissue with skin grafts). It may be concluded that serum G-CSF and IL-6 levels in burned patients may be considered as diagnostic factors, but the delays in the reaction to the massive infection do not allow us to use them for predicting the time of onset of the infection.

Topics: Adolescent; Adult; Aged; Burns; Child; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-4; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis

The precondition for the systematic modulation of host impairing behavior of hyperactivated monocytes following trauma is to fully understand the mechanistic basis of cellular dysfunction. It was the objective of this study to scrutinize the synthesis patterns and the level of regulation of the functionally related inflammatory cytokines interleukin (IL)-1 beta and IL-8 under stressful conditions. We compared the quantity of cytokine protein release in lipopolysaccharide-stimulated in vitro cultures of peripheral blood mononuclear leukocytes with the signal intensity of the corresponding detectable mRNAs. Fourteen patients with major burn or multiple trauma on consecutive days post-trauma and healthy volunteers were studied. We saw an almost identical pattern of synthesis for both monokines during the time of observation, with a considerable impairment until day 5 post-trauma and recovery thereafter. In contrast to IL-1 beta, a clear concurrence between mRNA signal intensity and the quantity of protein release was found in the majority of patients for IL-8. From these data we conclude that the launching mechanisms for the de novo synthesis for both monokines under stress differ greatly, with IL-8 being clearly regulated on the transcriptional level, whereas the downregulation of IL-1 beta occurs, most likely, on the post-transcriptional level.

Topics: Adolescent; Adult; Aged; Burns; Female; Humans; In Vitro Techniques; Inflammation Mediators; Interleukin-1; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Monocytes; RNA, Messenger; Time Factors; Transcription, Genetic; Wounds and Injuries

Progressive or ongoing skin necrosis after traumatic injury is well known. Experimental evidence has associated these events with neutrophil activation and secondary oxidant injury. To determine the mechanism by which neutrophils migrate to a site of injury, cytokine release from injured skin was measured.. Twenty-five skin biopsy specimens of acute partial thickness skin injuries were compared with uninjured skin of the same patient. Conditioned medium from explanted skin was assayed for tumor necrosis factor (TNF), interleukin-6 (IL-6), and IL-8.. Acute skin injury resulted in a significant release of IL-8 but not IL-6 or TNF. In eight patients gradient cytokine release was found; IL-8 levels for partial thickness burn were 26.4 ng/ml, for unburned skin adjacent to the burn were 2.1 ng/ml, and for distal normal skin were 0.2 ng/ml.. IL-8 is released from acutely injured skin; IL-6 and TNF are not. This selective release suggests a mechanism whereby neutrophils are recruited into injured tissue. These neutrophils might then induce further injury, increasing the extent of posttraumatic tissue loss.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Burns; Cells, Cultured; Chemotaxis, Leukocyte; Child; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutrophils; Skin; Tumor Necrosis Factor-alpha

Eighty-eight patients with acute thermal injury were evaluated. Forty-eight hours after injury, TNF, IL-6, and IL-8 were significantly present in the systemic circulation, lung, normal skin, and thermally injured skin. The presence of TNF, IL-6, and IL-8 proteins in the lung, normal skin, and thermally injured skin were associated with TNF, IL-6, and IL-8 mRNA upregulation. Logistic regression analysis controlling for the Abbreviated Burn Severity Index demonstrated that the presence of IL-8 in the lung was associated with early pulmonary physiologic dysfunction (p = 0.006) and nosocomial pulmonary infection (p = 0.040). We conclude that acute thermal injury initiates an early systemic, lung, and skin response involving TNF, IL-6, and IL-8. The TNF, IL-6, and IL-8 protein present in the lung and skin in response to acute thermal injury are generated locally and do not originate from the systemic cytokine pool. The lung cytokine response to acute thermal injury may initiate local organ failure.

Topics: Adult; Base Sequence; Burns; Dimercaprol; Female; Humans; Injury Severity Score; Interleukin-6; Interleukin-8; Lung; Male; Molecular Sequence Data; Polymerase Chain Reaction; Prospective Studies; RNA, Messenger; Skin; Time Factors; Tumor Necrosis Factor-alpha