Koller L D, Voller B E, Hedstrom O R, Steppan L G, Kerkvliet N I, Thueson D O
College of Veterinary Medicine, Oregon State University, Corvallis 97331-4801.
Int J Immunopharmacol. 1989;11(5):509-16. doi: 10.1016/0192-0561(89)90180-x.
The immunotoxic properties of two experimental antiallergic drugs, CI-949 and CI-959, were investigated. Wistar rats were gavaged once (CI-949) or twice (CI-959) daily for 21 days with the drugs. Immunotoxicity was assessed using the enzyme-linked immunoabsorbant assay (ELISA) for humoral immunity, a delayed-type hypersensitivity (DTH) procedure for cell-mediated immunity, and natural killer cell (NKC) activity to evaluate spontaneous cytotoxicity. Ratios of body weight to spleen, thymus, liver and kidney weights were determined. Routine histopathology was performed on lymphoid tissue and other body organs. Although 100 mg/kg/day of CI-949 had some stimulating effect on antibody production and NKC cytotoxicity, no consistent immunomodulation was apparent. Except for a significant increase in liver weight at the 100 mg/kg dose of CI-949, no other toxic effects were observed. In contrast to CI-949, CI-959 significantly (P less than 0.05) suppressed antibody production at the 100 mg/kg dose and impaired the DTH reaction, although not significantly. Natural killer cell cytotoxicity was unaffected by 100 mg/kg CI-959. Decreased body weight and histopathological lesions were observed in the thymus and spleen of rats administered 100 mg/kg CI-959. These lesions ranged from mild to severe lymphoid depletion which was also reflected in significantly (P less than 0.05) reduced spleen and thymus organ weight to body weight ratios. Since 100 mg/kg of CI-959 produced toxicological and pathological alterations in the exposed rats, these data suggest that CI-959 is not highly or specifically immunotoxic at dosages lower than those that alter conventional toxicological parameters used in new drug testing programs.(ABSTRACT TRUNCATED AT 250 WORDS)
对两种实验性抗过敏药物CI - 949和CI - 959的免疫毒性特性进行了研究。将Wistar大鼠每日灌胃一次（CI - 949）或两次（CI - 959），持续21天。使用酶联免疫吸附测定（ELISA）评估体液免疫的免疫毒性，采用迟发型超敏反应（DTH）程序评估细胞介导免疫，并用自然杀伤细胞（NKC）活性评估自发细胞毒性。测定体重与脾脏、胸腺、肝脏和肾脏重量的比值。对淋巴组织和其他身体器官进行常规组织病理学检查。尽管每天100 mg/kg的CI - 949对抗体产生和NKC细胞毒性有一定刺激作用，但未观察到一致的免疫调节作用。除了在100 mg/kg剂量的CI - 949下肝脏重量显著增加外，未观察到其他毒性作用。与CI - 949相反，100 mg/kg剂量的CI - 959显著（P小于0.05）抑制抗体产生并损害DTH反应，尽管不显著。100 mg/kg的CI - 959对自然杀伤细胞细胞毒性无影响。在给予100 mg/kg CI - 959的大鼠胸腺和脾脏中观察到体重减轻和组织病理学损伤。这些损伤范围从轻度到重度淋巴细胞耗竭，这也反映在脾脏和胸腺器官重量与体重比值显著（P小于0.05）降低。由于100 mg/kg的CI - 959在暴露的大鼠中产生了毒理学和病理学改变，这些数据表明，在低于改变新药测试程序中使用的传统毒理学参数的剂量下，CI - 959并非高度或特异性免疫毒性。（摘要截短为250字）
