Allo M, Silva J, Fekety R, Rifkin G D, Waskin H
Gastroenterology. 1979 Feb;76(2):351-5.
Toxins produced by Clostridium difficile have been implicated in the etiology of antibiotic-induced colitis. Clostridium difficile antitoxin is not available, but recent studies have shown that toxins present in the feces of patients with this disease are neutralized by Clostridium sordellii antitoxin. We found that C. sordellii antitoxin neutralized toxins produced in broth cultures of either C. sordellii or C. difficile and that passive immunization with C. sordellii antitoxin before challenge with clindamycin prevented colitis in hamsters. Significantly fewer antitoxin-treated animals than unimmunized controls developed diarrhea and died with hemorrhagic colitis. Administration of 300 U of antitoxin parenterally either on the day of challenge with clindamycin or 24 hr later provided significant protection (25% mortality vs. 100% mortality in controls, P less than 0.01). None of eight animals given antitoxin (300 U) both on the day of challenge and 24 hr later died. Filtrates prepared from cecal contents of dead or killed hamsters were tested for toxicity by intraperitoneal injection into hamsters and by addition to monolayers of monkey kidney cells. Fecal filtrates from antitoxin-protected animals were not toxic in these assays, but filtrates from control animals were uniformly toxic. Passive immunization against clostridial toxins was protective against clindamycin-associated colitis in this model. This finding further substantiates the importance of these toxins in the pathogenesis of antibiotic-induced colitis.
艰难梭菌产生的毒素与抗生素相关性结肠炎的病因有关。目前尚无艰难梭菌抗毒素，但最近的研究表明，该疾病患者粪便中的毒素可被索氏梭菌抗毒素中和。我们发现，索氏梭菌抗毒素可中和索氏梭菌或艰难梭菌肉汤培养物中产生的毒素，并且在用克林霉素攻击之前用索氏梭菌抗毒素进行被动免疫可预防仓鼠患结肠炎。接受抗毒素治疗的动物发生腹泻并死于出血性结肠炎的数量明显少于未免疫的对照组。在给予克林霉素攻击当天或24小时后经肠胃外给予300 U抗毒素可提供显著的保护作用（死亡率为25%，而对照组为100%，P<0.01）。在攻击当天和24小时后均给予抗毒素（300 U）的8只动物中无一死亡。通过腹腔注射到仓鼠体内以及添加到猴肾细胞单层中，对从死亡或处死的仓鼠盲肠内容物制备的滤液进行毒性测试。在这些试验中，来自抗毒素保护动物的粪便滤液无毒，但来自对照动物的滤液均具有毒性。在该模型中，针对梭菌毒素的被动免疫对克林霉素相关性结肠炎具有保护作用。这一发现进一步证实了这些毒素在抗生素相关性结肠炎发病机制中的重要性。
