Romani L, Puccetti P, Bistoni F
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Clin Microbiol Rev. 1997 Oct;10(4):611-36. doi: 10.1128/CMR.10.4.611.
Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that is crucially involved in a wide range of infectious diseases. In several experimental models of bacterial, parasitic, viral, and fungal infection, endogenous IL-12 is required for early control of infection and for generation and perhaps maintenance of acquired protective immunity, directed by T helper type 1 (Th1) cells and mediated by phagocytes. Although the relative roles of IL-12 and gamma interferon in Th1-cell priming may be to a significant extent pathogen dependent, common to most infections is that IL-12 regulates the magnitude of the gamma interferon response at the initiation of infection, thus potentiating natural resistance, favoring Th1-cell development; and inhibiting Th2 responses. Treatment of animals with IL-12, either alone or as a vaccine adjuvant, has been shown to prevent disease by many of the same infectious agents, by stimulating innate resistance or promoting specific reactivity. Although IL-12 may enhance protective memory responses in vaccination or in combination with antimicrobial chemotherapy, it is yet unclear whether exogenous IL-12 can alter established responses in humans. Continued investigation into the possible application of IL-12 therapy to human infections is warranted by the role of the cytokine in inflammation, immunopathology, and autoimmunity.
白细胞介素-12(IL-12)是一种强效免疫调节细胞因子,在多种传染病中起着至关重要的作用。在细菌、寄生虫、病毒和真菌感染的多个实验模型中,内源性IL-12是早期控制感染以及由1型辅助性T细胞(Th1)细胞主导并由吞噬细胞介导的获得性保护性免疫的产生及可能的维持所必需的。尽管IL-12和γ干扰素在Th1细胞启动中的相对作用在很大程度上可能取决于病原体,但大多数感染的共同之处在于,IL-12在感染开始时调节γ干扰素反应的强度,从而增强天然抵抗力,促进Th1细胞发育,并抑制Th2反应。单独使用IL-12或作为疫苗佐剂对动物进行治疗,已显示可通过刺激先天抵抗力或促进特异性反应性来预防许多相同传染源引起的疾病。尽管IL-12可能会增强疫苗接种或与抗菌化疗联合使用时的保护性记忆反应,但尚不清楚外源性IL-12是否能改变人类已有的反应。鉴于该细胞因子在炎症、免疫病理学和自身免疫中的作用,有必要继续研究IL-12疗法在人类感染中的可能应用。