Tambourgi D V, Petricevich V L, Magnoli F C, Assaf S L, Jancar S, Dias Da Silva W
Laboratory of Immunochemistry, Instituto Butantan, São Paulo, SP, Brazil.
Toxicon. 1998 Feb;36(2):391-403. doi: 10.1016/s0041-0101(97)00063-9.
The systemic symptoms, tissue lesions and release of cytokines were analysed in four isogenic mouse strains with distinct haplotypes injected with various doses of Loxosceles intermedia spider venom. The estimated LD50 were 24.5 microg for C57Bl/6, 17.6 microg for BALB/c, 6.3 microg for C3H/HeJ and 4.6 microg for A/Sn mice. Prostration, acute cachexia, hypothermia, neurological disorders and hemoglobinuria were the signals preceding death. Accumulation of eosinophilic material inside the proximal and distal renal tubules and acute tubular necrosis were the most common histopathological findings. Death was prevented by previous treatment of venom with specific antivenom serum. The protein F35 purified from the whole venom retained the ability to induce the symptoms of the whole venom. The cytokines tumor necrosis factor (TNF), interleukins IL-6 and IL-10 and the radical nitric oxide were detected in serum at different levels after venom injection. These findings indicate that the state of shock produced in mice by whole endotoxin-free L. intermedia venom or by its purified fraction, protein F35, mimics the endotoxemic shock, that susceptibility to the systemic effects of the venom varies among mice of different haplotypes and that the pattern of in vivo cytokine release resembles that of endotoxemic shock.
对四种具有不同单倍型的同基因小鼠品系注射不同剂量的巴西游走蛛毒液后，分析其全身症状、组织损伤和细胞因子释放情况。C57Bl/6小鼠的估计半数致死量（LD50）为24.5微克，BALB/c小鼠为17.6微克，C3H/HeJ小鼠为6.3微克，A/Sn小鼠为4.6微克。虚脱、急性恶病质、体温过低、神经功能障碍和血红蛋白尿是死亡前的信号。近端和远端肾小管内嗜酸性物质的积聚以及急性肾小管坏死是最常见的组织病理学发现。用特异性抗蛇毒血清预先处理毒液可预防死亡。从全毒液中纯化的蛋白质F35保留了诱导全毒液症状的能力。注射毒液后，血清中检测到不同水平的细胞因子肿瘤坏死因子（TNF）、白细胞介素IL-6和IL-10以及自由基一氧化氮。这些发现表明，无内毒素的巴西游走蛛全毒液或其纯化组分蛋白质F35在小鼠中产生的休克状态类似于内毒素血症休克，不同单倍型小鼠对毒液全身作用的易感性不同，且体内细胞因子释放模式类似于内毒素血症休克。
