Pathogenic role of interleukin-6 in the development of sepsis. Part I: Study in a standardized contact burn murine model
| Autor: | Dennis von Heimburg, Norbert Pallua |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Male Burn injury Time Factors Lipopolysaccharide Body Surface Area medicine.medical_treatment Pharmacology Critical Care and Intensive Care Medicine Sepsis Interferon-gamma Leukocyte Count Mice chemistry.chemical_compound Animals Medicine Pseudomonas Infections Platelet Interleukin 6 Inflammation biology Interleukin-6 Platelet Count Tumor Necrosis Factor-alpha business.industry Interleukin medicine.disease Receptors Interleukin-6 Mice Inbred C57BL Disease Models Animal Cytokine chemistry Immunology biology.protein Tumor necrosis factor alpha Burns business |
| Zdroj: | Critical Care Medicine. 31:1490-1494 |
| ISSN: | 0090-3493 |
| Popis: | OBJECTIVE To establish a representative model for the evaluation of interleukin (IL)-6 and IL-6 receptor for pathogenicity and lethality in the postburn period. DESIGN Ten-week-old C 57 BL/6J mice received a 20% body surface area contact burn and/or lipopolysaccharide (LPS) 48 hrs later. Standardized burns were created with a metal stamp of 150 degrees C of defined pressure and surface area (2.4525 Newton/0.00166 m2) over a period of 11 secs. The depth of dermal injury was verified histologically. The following groups were formed: I: no burn, no LPS (n = 35); II: burn, no LPS (n = 140); III, no burn, LPS (n = 56); and IV, burn, LPS (n = 80), to study the effect of burn alone, sepsis alone, or the combination. Lethal LPS dose (LD100) was determined by application of LPS in increasing doses (200, 300, 400, and 500 microg, n = 32) after burns. MEASUREMENTS Concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), and leukocytes, platelets and organ pathology were evaluated. SETTING Research laboratory. RESULTS Burn and LPS showed an additive effect on the release of IL-6 but not of TNF-alpha and IFN-gamma. Leukocyte and platelet numbers decreased significantly (group IV) compared with the other groups (I-III). The maximal levels of IL-6 in group IV were reached earlier than those of TNF-alpha. The contact burn model has a mortality rate of 30%, which is close to clinical outcome. We found the model of contact burn superior to scald or flame burn models. A dose of 400-microg LPS was found to be the lethal LPS dose (LD100). CONCLUSIONS Our data suggest that preexisting burn injury increases the response to endotoxin. TNF-alpha is not involved in priming. IL-6 on the other hand is a very representative parameter for priming. Because TNF-alpha was obviously not the causative factor, it was concluded that the application of anti-IL-6-mAb should be of great value. Therefore, a therapeutic application was designed, see part II. |
| Databáze: | OpenAIRE |
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