The two faces of interleukin 12: a pro-inflammatory cytokine and a key immunoregulatory molecule produced by antigen-presenting cells.
The two faces of interleukin 12: a pro-inflammatory cytokine and a key immunoregulatory molecule produced by antigen-presenting cells.
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DOI：
10.1002/9780470514849.ch14
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
G. Trinchieri
中科院分区：
文献类型：
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作者：
G. Trinchieri
白细胞介素12（IL-12）由吞噬细胞、抗原呈递细胞和B淋巴细胞响应细菌或细胞内寄生虫而产生。IL-12作用于T和自然杀伤（NK）细胞，诱导：细胞因子，特别是γ-干扰素（IFN-γ）的产生;增殖;和细胞介导的细胞毒性的增强。在感染早期，IL-12作为促炎细胞因子并诱导NK和T细胞产生IFN-γ。IFN-γ激活吞噬细胞并增加其产生IL-12的能力。与IFN-γ不同，IL-10、IL-4、IL-13和转化生长因子β是IL-12的产生和活性的负调节剂。IL-12通过刺激T辅助1（Th 1）细胞的产生为随后的适应性免疫应答奠定基础。IL-12（有利于Th 1应答）和IL-4（有利于Th 2应答）之间的平衡可能决定了免疫应答期间Th 1/Th 2二分法的最终结果。HIV感染患者即使在疾病的早期阶段也缺乏IL-12的产生。然而，外源性IL-12可以在体外改善这些患者的T和NK细胞的免疫应答性缺陷，这表明IL-12缺陷在HIV疾病发病机制中的可能作用以及IL-12对机会性病原体和HIV感染本身的潜在治疗作用。
Interleukin 12 (IL-12) is produced by phagocytic cells, antigen-presenting cells and B lymphocytes in response to bacteria or intracellular parasites. IL-12 acts on T and natural killer (NK) cells inducing: production of cytokines, particularly gamma-interferon (IFN-gamma); proliferation; and enhancement of cell-mediated cytotoxicity. Early in infection, IL-12 acts as a proinflammatory cytokine and induces IFN-gamma production by NK and T cells. IFN-gamma activates the phagocytes and increases their ability to produce IL-12. Unlike IFN-gamma, IL-10, IL-4, IL-13 and transforming growth factor beta are negative regulators of the production and activity of IL-12. IL-12 sets the stage for the ensuing adaptive immune response by stimulating the generation of T helper 1 (Th1) cells. It is likely that the balance between IL-12 (favouring a Th1 response) and IL-4 (favouring a Th2 response) determines the eventual outcome of the Th1/Th2 dichotomy during an immune response. HIV-infected patients have a deficient production of IL-12, even at early stages of the disease. However, exogenous IL-12 can improve the deficient immune responsiveness of these patients' T and NK cells in vitro, suggesting a possible role of the IL-12 deficiency in HIV disease pathogenesis and a potential therapeutic role of IL-12 both against opportunistic pathogens and HIV infection itself.