ObjectiveTo establish a representative model for the evaluation of interleukin (IL)-6 and IL-6 receptor for pathogenicity and lethality in the postburn period.DesignTen-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°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 &mgr;g, n = 32) after burns.MeasurementsConcentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-&agr;) and interferon-gamma (IFN-&ggr;), and leukocytes, platelets and organ pathology were evaluated.SettingResearch laboratory.ResultsBurn and LPS showed an additive effect on the release of IL-6 but not of TNF-&agr; and IFN-&ggr;. 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-&agr;. 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-&mgr;g LPS was found to be the lethal LPS dose (LD100).ConclusionsOur data suggest that preexisting burn injury increases the response to endotoxin. TNF-&agr; is not involved in priming. IL-6 on the other hand is a very representative parameter for priming. Because TNF-&agr; 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.