Carneiro Adriana S, Ribeiro Orlando G, De Franco Marcelo, Cabrera Wafa H K, Vorraro Francisca, Siqueira Maria, Ibañez Olga M, Starobinas Nancy
Laboratório de Imunogenética, Instituto Butantan, Av Vital Brasil 1500-cep 05503-900 São Paulo, SP, Brazil.
Toxicon. 2002 Nov;40(11):1571-9. doi: 10.1016/s0041-0101(02)00174-5.
Bothrops jararaca venom (BjV) causes severe systemic and local reactions, characterized by an acute inflammatory reaction with accumulation of leukocytes and release of endogenous mediators. The systemic and local effects of BjV were compared in lines of mice genetically selected for maximal (AIR(max)) or minimal (AIR(min)) acute inflammatory reactivity (AIR). The systemic reaction was evaluated by LD(50) and the local reaction by edema formation, cellular influx, release of PGE(2), NO and H(2)O(2) and the production of the pro-inflammatory cytokines IL-6, Tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Both mouse lines were equally susceptible to the lethal effects of the venom showing similar LD(50) but differed significantly in terms of the local inflammatory reaction. Footpad edema and leukocyte influx in the peritoneum after BjV inoculation was higher in AIR(max) compared to AIR(min), BALB/c or outbred Swiss mice. Coincidently, higher levels of the soluble mediators PGE(2), IFN-gamma and TNF-alpha were detected in the inflammatory exudate induced by BjV in AIR(max) mice. Cytokines levels were correlated to in vitro NO and H(2)O(2) production. The results demonstrate that the genetic factors selected in AIR(max) and AIR(min) lines of mice interfere in the control of the acute local reaction triggered by BjV venom.
巴西矛头蝮蛇毒（BjV）会引发严重的全身和局部反应，其特征为伴有白细胞聚集和内源性介质释放的急性炎症反应。在经过基因筛选以获得最大（AIR(max)）或最小（AIR(min)）急性炎症反应性（AIR）的小鼠品系中，对BjV的全身和局部效应进行了比较。通过半数致死剂量（LD(50)）评估全身反应，通过水肿形成、细胞浸润、前列腺素E2（PGE(2)）、一氧化氮（NO）和过氧化氢（H(2)O(2)）的释放以及促炎细胞因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的产生来评估局部反应。两种小鼠品系对蛇毒的致死效应同样敏感，表现出相似的LD(50)，但在局部炎症反应方面存在显著差异。与AIR(min)、BALB/c或远交系瑞士小鼠相比，接种BjV后，AIR(max)小鼠的足垫水肿和腹膜白细胞浸润更高。巧合的是，在AIR(max)小鼠中，由BjV诱导的炎症渗出物中检测到更高水平的可溶性介质PGE(2)、IFN-γ和TNF-α。细胞因子水平与体外NO和H(2)O(2)的产生相关。结果表明，在AIR(max)和AIR(min)小鼠品系中选择的遗传因素会干扰由BjV毒液引发的急性局部反应的控制。
