The venom of South American rattlesnakes inhibits macrophage functions and is endowed with anti‐inflammatory properties

Abstract

The injection of Crotalus durissus terrificus venom into the foot pad of mice did not induce a significant inflammatory response as evaluated by oedema formation, increased vascular permeability and cell migration. The subcutaneous injection of the venom, or its addition to cell cultures, had an inhibitory effect on the spreading and phagocytosis of resident macrophages, without affecting the viability of the cells. This effect was not observed when the venom was added to cultures of thioglycollate elicited macrophages, but it was able to inhibit these macrophage functions when the cells were obtained from animals injected simultaneously with the venom and thioglycollate. These observations suggest that the venom interferes with the mechanisms of macrophage activation. Leukocyte migration induced by intraperitoneal injection of thioglycollate was also inhibited by previous venom injection. This down-regulatory activity of the venom on macrophage functions could account for the mild inflammatory response observed in the site of the snake bite in Crotalus durissus terrificus envenomation in man.

Crotoxin Isolated fromCrotalus durissus terrificusVenom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors

“…In addition, it was observed a lower proliferation of T lymphocytes from the mice immunized with HSA/CFA or HSA/Alum and that received the toxin, in response to the stimulation either by HSA or mitogen. As well, it was shown that CTX modulates the macrophage and neutrophil activities and this effect involves lipoxin secretion and the formyl peptide receptors (FPRs) [ 31 – 34 ]. Our group also demonstrated that the increased secretion of lipoxin A 4 is associated with decreased secretion of cytokines TNF- α , IL-1 β , and IL-6 as well as an increase of CD4 + FoxP3 + population, which are important for the inhibitory effect of CTX on the acute inflammatory intestinal reaction induced by the intrarectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice [ 35 ].…”

Immunotherapeutic potential of Crotoxin: anti-inflammatory and immunosuppressive properties

“…Aside from clinical data, experimental reports on basic research have also demonstrated that C.d.t. venom is responsible for inducing anti-inflammatory, immunosuppressive and analgesic effects [28–32]. Therefore, since the late 1980’s, toxinologists in the immunology field have been focusing in Crotoxin’s participation in both innate and adaptative immunity.…”

“…Studies have shown that C.d.t. venom is able to reduce both carrageenan, bacillus Calmette-Guérin (BCG) and thioglycolate-induced mice paw edema and polymorphonuclear leukocyte infiltration [28, 32, 49]. Interestingly, C.d.t.…”

“…C.d.t. venom induced a significant inhibition of spreading and phagocytic activity of peritoneal macrophages both in vitro and in vivo [28, 50]. This suppressant behavior also presented a long-lasting effect with macrophages treated with venom 16 days before spreading and phagocytosis stimulation [28].…”

Ausência de efeito antinociceptivo decorrente da administração intravenosa de crotalfina em comparação com morfina, U50-488H ou fenilbutazona em equinos submetidos à estimulação térmica da pele íntegra

“…Segundo Vital Brazil relatou na primeira metade do século XX, vítimas de acidente crotálico não apresentavam reação infl amatória intensa e relatavam analgesia local (SOUSA & SILVA et al, 1996). Posteriormente, identifi cou-se a presença de peptídeo opioide no veneno de Crotalus durissus terrifi cus e a aplicação deste em ratos promove analgesia signifi cativa e prolongada em modelos de dor infl amatória (BRIGATTE et al, 2001), neuropática (GUTIERREZ, 2005) e oncológica (BRIGATTE et al, 2004).…”