Brunda M J
Department of Oncology, Hoffman-LaRoche, Inc., Nutley, NJ 07110.
J Leukoc Biol. 1994 Feb;55(2):280-8. doi: 10.1002/jlb.55.2.280.
Interleukin-12 (IL-12) is a newly characterized cytokine that has a unique heterodimeric structure. It was initially cloned from B lymphoblastoid cell lines, but the majority of IL-12 is produced by macrophages/monocytes following appropriate stimulation. IL-12 can (1) enhance the cytolytic activity of a number of effector cells including T cells, natural killer (NK) cells, lymphokine activated killer (LAK) cells, and macrophages, (2) increase proliferation of activated NK and T cells, (3) induce production of cytokines, such as interferon gamma, (4) stimulate the induction of TH1 cells, (5) upregulate a number of cell surface molecules, (6) inhibit IgE secretion, and (7) act as a synergistic factor for hematopoietic stem cells. Based on these potent immunomodulatory activities, IL-12 has been evaluated in several disease models for parasitic infections and malignancies. Marked activity of IL-12 against both Leishmania and Toxoplasma has been reported. Likewise, antimetastatic and antitumor activity, including tumor regression, has been observed against a number of murine malignancies treated with IL-12 using doses that result in little toxicity. The results suggest that IL-12 may be a useful cytokine for the treatment of a number of diseases.
白细胞介素-12（IL-12）是一种新发现的具有独特异二聚体结构的细胞因子。它最初是从B淋巴母细胞系中克隆出来的，但大多数IL-12是巨噬细胞/单核细胞在适当刺激后产生的。IL-12可以：（1）增强包括T细胞、自然杀伤（NK）细胞、淋巴因子激活的杀伤（LAK）细胞和巨噬细胞在内的多种效应细胞的细胞溶解活性；（2）增加活化的NK细胞和T细胞的增殖；（3）诱导细胞因子如干扰素γ的产生；（4）刺激TH1细胞的诱导；（5）上调多种细胞表面分子；（6）抑制IgE分泌；（7）作为造血干细胞的协同因子。基于这些强大的免疫调节活性，IL-12已在几种寄生虫感染和恶性肿瘤疾病模型中进行了评估。据报道，IL-12对利什曼原虫和弓形虫均有显著活性。同样，使用几乎无毒性剂量的IL-12治疗多种小鼠恶性肿瘤时，观察到了抗转移和抗肿瘤活性，包括肿瘤消退。结果表明，IL-12可能是治疗多种疾病的一种有用的细胞因子。
