Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom

WE have provided evidence that: (a) lethality of mice to crude Bothrops ven om varies according the isogenic strain (A/J > C57B1/6 > A/Sn > BALB/c > C3 H/HePas > DBA/2 > C3H/He); (b)BALB/c mice (LD50=100.0 mu g) were injected i .p. with 50 mu g of venom produced IL-6, IL-IO, INF-gamma, TNF-alpha and NO in the serum. In vitro the cells from the mice injected and challenged wit h the venom only released IL-10 while peritoneal macrophages released IL-10 , INF-gamma and less amounts of IL-6; (c) establishment of local inflammati on and necrosis induced by the venom, coincides with the peaks of TNF-alpha , IFN-gamma and NO and the damage was neutralized when the venom was incuba ted with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops atrox venom is genetically dependent but MHC independent; that IL-6, IL-10, TNF-alpha, IFN-gamma and N O can be involved in the mediation of tissue damage; and that the major ven om component inducers of the lesions are haemorrhagins.