ENDOTOXEMIC-LIKE SHOCK-INDUCED BY LOXOSCELES SPIDER VENOMS - PATHOLOGICAL-CHANGES AND PUTATIVE CYTOKINE MEDIATORS

The systemic symptoms, tissue lesions and release of cytokines were an alysed in four isogenic mouse strains with distinct haplotypes injecte d with various doses of Loxosceles inter media spider venom. The estim ated LD50 were 24.5 mu g for C57B1/6, 17.6 mu g for BALB/c, 6.3 mu g f or C3H/HeJ and 4.6 mu g for A/Sn mice. Prostration, acute cachexia, hy pothermia, neurological disorders and hemoglobinuria were the signals preceding death. Accumulation of eosinophilic material inside the prox imal and distal renal tubules and acute tubular necrosis were the most common histopathological findings. Death was prevented by previous tr eatment of venom with specific antivenom serum. The protein F35 purifi ed from the whole venom retained the ability to induce the symptoms of the whole venom. The cytokines tumor necrosis factor (TNF), interleuk ins IL-6 and IL-10 and the radical nitric oxide were detected in serum at different levels after venom injection. These findings indicate th at the state of shock produced in mice by whole endotoxin-free L. inte rmedia in venom or by its purified fraction, protein F35, mimics the e ndotoxemic shock, that susceptibility to the systemic effects of the v enom varies among mice of different haplotypes and that the pattern of in vivo cytokine release resembles that of endotoxemic shock. (C) 199 8 Elsevier Science Ltd. All rights reserved.