Petricevich V L, Teixeira C F, Tambourgi D V, Gutiérrez J M
Laboratories of Immunochemistry, Av. Vital Brazil 1500, CEP 05504-900, São Paulo, Brazil.
Toxicon. 2000 Sep;38(9):1253-66. doi: 10.1016/s0041-0101(99)00227-5.
Changes in serum levels of several cytokines and nitric oxide were studied in BALB/c mice injected intraperitoneally with one median lethal dose (LD(50)) of the venoms of Bothrops asper and Bothrops jararaca, two of the medically most important poisonous snakes of Latin America. Despite differences observed in the time-course of cytokine increments and in serum cytokine levels, both venoms induced prominent elevations of TNF-alpha, IL-1, IL-6, IL-10 and IFN-gamma. There was an early increase in TNF-alpha and IL-1, followed 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 venom. Serum nitric oxide concentration increased in mice injected with both venoms rapidly after envenomation, remaining elevated for 24 h. It is concluded that a complex pattern of cytokine and nitric oxide synthesis and secretion occurs in severe experimental envenomation by B. asper and B. jararaca venoms. Furthermore, it is suggested that some of these mediators, particularly TNF-alpha, IL-1 and nitric oxide, might play a relevant role in the pathophysiology of systemic alterations induced by these venoms.
在腹腔注射了拉丁美洲两种医学上最重要的毒蛇——矛头蝮蛇和巴西矛头蝮蛇毒液的半数致死剂量（LD(50)）的BALB/c小鼠中，研究了几种细胞因子和一氧化氮的血清水平变化。尽管在细胞因子增加的时间进程和血清细胞因子水平上观察到差异，但两种毒液均引起肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和干扰素-γ（IFN-γ）显著升高。TNF-α和IL-1早期增加，随后在18小时时增加更为明显。IL-6水平在4至6小时达到峰值，这种细胞因子可能调节TNF-α和IL-1的分泌以及急性期蛋白的合成。两种毒液均诱导血清IL-10早期增加，而注射巴西矛头蝮蛇毒液的小鼠中IFN-γ水平高于注射矛头蝮蛇毒液的小鼠。注射两种毒液的小鼠在中毒后血清一氧化氮浓度迅速增加，并在24小时内保持升高。结论是，在由矛头蝮蛇和巴西矛头蝮蛇毒液引起的严重实验性中毒中，发生了细胞因子和一氧化氮合成与分泌的复杂模式。此外，有人提出，这些介质中的一些，特别是TNF-α、IL-1和一氧化氮，可能在这些毒液引起的全身改变的病理生理学中起相关作用。
