Increments in serum cytokine and nitric oxide levels in mice injected withBothrops asper and Bothrops jararaca snake venoms

Changes in serum levels of several cytokines and nitric oxide were studied in BALB/c mice injected intraperitoneally with one median lethal dose (LD50 ) of the venoms of Bothrops asper and Bothrops jararaca, two of the medical ly most important poisonous snakes of Latin America. Despite differences ob served in the time-course of cytokine increments and in serum cytokine leve ls, both venoms induced prominent elevations of TNF-alpha, IL-1, IL-6, IL-1 0 and IFN-gamma. There was an early increase in TNF-alpha and IL-1, followe d by a more pronounced increment by 18 h. IL-6 levels peaked-between 4 and 6 h, and this cytokine probably modulates the secretion of TNF-alpha and IL -1 and the synthesis of acute-phase proteins, Both venoms induced an early increment in serum IL-10, whereas IFN-gamma levels reached higher values in mice injected with B. jararaca venom than in those receiving B. asper veno m, Serum nitric oxide concentration increased in mice injected with both ve noms rapidly after envenomation, remaining elevated for 24 h. It is conclud ed that a complex pattern of cytokine and nitric oxide synthesis and secret ion occurs in severe experimental envenomation by B, asper and B. jararaca venoms. Furthermore, it is suggested that some of these mediators, particul arly TNF-alpha, IL-1 and nitric oxide, might play a relevant role in the pa thophysiology of systemic alterations induced by these venoms. (C) 2000 Els evier Science Ltd. All rights reserved.