Kohl S, Sigaroudinia M, Charlebois E D, Jacobson M A
Department of Pediatrics, University of California, San Francisco, USA.
J Infect Dis. 1996 Nov;174(5):1105-8. doi: 10.1093/infdis/174.5.1105.
Persons infected with human immunodeficiency virus (HIV) have cellular cytotoxicity defects. Interleukin (IL)-12 is a potent stimulator of cytotoxicity. Fifteen HIV-infected patients were studied in a phase 1, single-dose escalation trial of human recombinant IL-12. One day after subjects received an IL-12 dose of 300 or 1000 ng/kg, they had a reduction in absolute lymphocyte count and peripheral blood mononuclear cell recovery. In evaluable patients 24 h after IL-12 administration, there was a 31% reduction overall in NK cell cytotoxicity (NKC) to HIV-infected cells at all doses and a 52% reduction in antibody-dependent cellular cytotoxicity (ADCC) at doses of 300 and 1000 ng/kg. In vitro incubation of patients' cells with IL-12 (before IL-12 administration) for 24 h increased NKC but had no effect on ADCC. The paradoxic acute reduction in cell number and cytotoxicity in vivo may be due to NK cell trafficking or regulatory cytokine mechanisms not apparent in vitro.
感染人类免疫缺陷病毒（HIV）的个体存在细胞毒性缺陷。白细胞介素（IL）-12是一种强大的细胞毒性刺激物。在一项关于重组人IL-12的1期单剂量递增试验中，对15名HIV感染患者进行了研究。受试者接受300或1000 ng/kg的IL-12剂量一天后，其绝对淋巴细胞计数和外周血单个核细胞恢复情况有所下降。在IL-12给药24小时后可评估的患者中，所有剂量下对HIV感染细胞的自然杀伤细胞毒性（NKC）总体下降31%，在300和1000 ng/kg剂量下，抗体依赖性细胞毒性（ADCC）下降52%。在体外将患者细胞与IL-12（在IL-12给药前）孵育24小时可增加NKC，但对ADCC无影响。体内细胞数量和细胞毒性的反常急性下降可能是由于NK细胞转运或调节性细胞因子机制在体外不明显。
