Abstract
Crotoxin (CTX) is a potent neurotoxin from Crotalus durissus terrificus snake venom (CdtV) composed of two subunits: one without catalytic activity (crotapotin), and a basic phospolipase A2. Recent data have demonstrated that CdtV or CTX inhibit some immune and inflammatory reactions. The aim of this paper was to investigate the mechanisms involved in these impaired responses. Male Swiss mice were bled before and at different intervals of time after subcutaneous injection of CTX or bovine serum albumin (BSA) (control animals). The effect of treatments on circulating leukocyte mobilisation and on serum levels of interleukin (IL)-6, IL-10, interferon (IFN)-gamma and corticosterone were investigated. Spleen cells from treated animals were also stimulated in vitro with concanavalin A to evaluate the profile of IL-4, IL-6, IL-10 or IFN-gamma secretion. Cytokine levels were determined by immunoenzymatic assay and corticosterone levels by radioimmunoassay. To investigate the participation of endogenous corticosteroid on the effects evoked by CTX, animals were treated with metyrapone, an inhibitor of glucocorticoid synthesis, previous to CTX treatment. Marked alterations on peripheral leukocyte distribution, characterised by a drop in the number of lymphocytes and monocytes and an increase in the number of neutrophils, were observed after CTX injection. No such alteration was observed in BSA-treated animals. Increased levels of IL-6, IL-10 and corticosterone were also detected in CTX-injected animals. IFN-gamma levels were not modified after treatments. In contrast, spleen cells obtained from CTX-treated animals and stimulated with concanavalin A secreted less IL-10 and IL-4 in comparison with cells obtained from control animals. Metyrapone pretreatment was effective only to reverse the neutrophilia observed after CTX administration. Our results suggest that CTX may contribute to the deficient inflammatory and immune responses induced by crude CdtV. CTX induces endogenous mechanisms that are responsible, at least in part, for these impaired responses.
Highlights
Crotoxin (CTX), a b -neurotoxin from the venom of South American rattlesnake Crotalus durissus terrificus, is responsible for neuromuscular transmission blocking, myotoxic effects and lethality induced in vivo by the venom.[1,2]
In spite of its high phospholipase A2 (PLA2) content, crude Crotalus durissus terrificus snake venom (CdtV) induces a short-duration oedema,[8,9] a scarce cell infiltration in subcutaneous tissues, and inhibits some activities displayed by inflammatory macrophages.[8]
The data presented in this study suggest that CTX is able to evoke endogenous mechanisms, such as the reduction of mononuclear cells on circulation and secretion of anti-inflammatory cytokines and glucocorticoids, that may contribute to the lack of local inflammatory reaction during envenomation by CdtV and to the immunosuppression evoked by this venom
Summary
In spite of its high PLA2 content, crude Crotalus durissus terrificus snake venom (CdtV) induces a short-duration oedema,[8,9] a scarce cell infiltration in subcutaneous tissues, and inhibits some activities displayed by inflammatory macrophages.[8] In addition, it has been demonstrated that CTX or CdtV. Results: Marked alterations on peripheral leukocyte distribution, characterised by a drop in the number of lymphocytes and monocytes and an increase in the number of neutrophils, were observed after CTX injection. No such alteration was observed in BSAtreated animals. CTX induces endogenous mechanisms that are responsible, at least in part, for these impaired responses
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