The immunomodulatory effect of montiviperabornmuelleri [sic] montivipera bornmuelleri venom on the levels of various cytokines in the spleens of mice

Abstract

Snake venom serves as a tool of defense against threat and helps in prey digestion. It consists of a mixture of toxic proteins and enzymes. Beside their toxicity, venom components possess many pharmacological effects and have been used to design drugs and as biomarkers of diseases. Montivipera bornmuelleri belongs to the snake family of Vipiridae, whose venom in mainly hemotoxic. The snake is endemic to Lebanese mountains and recorded at altitudes exceeding 1800m. Biological characterization of M.bornmuelleri venom showed that it exhibits antibacterial, vasorelaxant, pro- and anti-coagulant as well as inflammatory activities in vitro. Literature has mainly focused on determining the effect of several snake venoms on the immune system of mice; however, that of M. bornmuelleri has not been established yet. This study investigates the immunomodulatory effects of M. bornmuelleri venom in vivo on the splenic levels of TNF-α, IFN-γ, IL-4, IL-10, IL-1ß and IL-17 in mice at 6 and then at24 hours post treatment. Different doses of venom (25µg, 50µg, 100µg and 150µg) were injected intraperitoneally in BALB/c mice. Recording the proportion of dead mice for each dose by 24 hours allowed calculating the median lethal dose of the venom. Using the logit method, LD50 of M. bornmuelleri was proved to be equal to 47.9 µg/mice in our experimental conditions. Quantitative measurement of cytokines was assessed using ELISA kits. As compared to the control, both doses 25µg and 50µg of venom modulated the levels of cytokines along a different time course. In general, M. bornmuelleri venom up-regulated the levels of the proinflammatory cytokines TNF-α, IFN-γ, IL-1ß and IL-17 and established a trend in decreasing the anti-inflammatory cytokine IL-10. By shifting inflammation towards a dominant Th1/Th17 rather than a Th2/Treg response, the venom of interest might possibly activate antitumor immunity, break tumor tolerance and thus potentially be a novel therapeutic in the growing field of cancer immunotherapy.