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目的:观察重组人白细胞介素-12(rhIL-12)对食蟹猴的长期毒性。方法:食蟹猴皮下注射给予rhIL-12,剂量分别为0.5,5和40μg·kg-1,每周3次,共13周。检测指标包括临床症状、血液学、血生化、免疫、血清抗体和组织病理学检查。结果:rhIL-12给药后导致动物出现腹泻、面部及眼睑部肿胀、腹股沟淋巴结肿大、溃疡、及注射局部红斑和硬结等临床症状,并出现贫血和白细胞分类异常,血液生化指标出现肝脏转氨酶升高,免疫学指标出现外周血总T淋巴细胞比例增加,CD4细胞百分率下降,CD8细胞百分率增加。第7次给药后,给药组动物产生了rhIL-12抗体。结论:食蟹猴皮下注射给予rhIL-12,毒性靶器官和组织为血液系统、肝脏、心脏、肾脏和淋巴结等免疫调节系统,其安全剂量为0.5μg·kg-1。
Objective: To observe the long-term toxicity of recombinant human interleukin-12 (rhIL-12) to cynomolgus monkeys. METHODS: Cynomolgus monkey was injected subcutaneously with rhIL-12 at dosage of 0.5, 5 and 40 μg · kg-1, three times a week for 13 weeks. Test indicators include clinical symptoms, hematology, blood biochemistry, immunity, serum antibodies and histopathological examination. Results: RhIL-12 resulted in diarrhea, swollen facial and eyelid, swollen inguinal lymph nodes, ulceration, and local erythema and induration of injection. The symptoms of anemia and leucocyte were abnormal. Blood aminotransferase Increased, immunological indicators of peripheral blood total T lymphocytes increased, the percentage of CD4 cells decreased, the percentage of CD8 cells increased. After the seventh administration, rhIL-12 antibody was produced in the animals in the administration group. CONCLUSIONS: Cynomolgus monkey is given rhIL-12 by subcutaneous injection. Its target organs and tissues are immunosuppressive system such as blood system, liver, heart, kidney and lymph nodes. The safe dose is 0.5μg · kg-1.