The Possible Role of Interleukin (IL)-12 and Interferon-γ-Inducing Factor/IL-18 in Protection against ExperimentalMycobacterium lepraeInfection in Mice

Kazuo Kobayashi , Masanori Kai , Masa-ichi Gidoh , Noboru Nakata , Masumi Endoh , Ram Pyare Singh , Tsuyoshi Kasama , Hajime Saito
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引用次数: 80

Abstract

Cell-mediated immunity participates in host defense against mycobacterial infection. Both interleukin 12 (IL-12) and interferon-γ-inducing factor (IGIF/IL-18), produced mainly by macrophages, play a critical role in expression of cell-mediated immunity. To investigate the role of IL-12 and IGIF/IL-18in vivo,we examined cytokine profile, bacterial growth, and the potential benefit of cytokine therapy in susceptible and resistant mice infected withMycobacterium leprae.The early expression of IL-12 p40 and IGIF/IL-18 at the site of inoculation was found in resistant mice 3–72 h after the infection, but not in susceptible mice. Both strains of mice did not show expression of IFN-γ and IL-4. IL-12 administration resulted in a significant reduction of bacterial counts in mice with establishedM. lepraeinfection. The results imply that susceptible mice exhibit decreased expression of type 1 helper T (Th1) response without reciprocal increased Th2 response and show responsiveness to exogenous IL-12. IL-12 therapy may be a possible rationale for treatment ofM. lepraeinfection.

白细胞介素(IL)-12和干扰素-γ诱导因子/IL-18在小鼠实验性麻风分枝杆菌感染中的可能作用
细胞介导的免疫参与宿主对分枝杆菌感染的防御。白细胞介素12 (IL-12)和干扰素γ诱导因子(IGIF/IL-18)主要由巨噬细胞产生,在细胞介导免疫的表达中起关键作用。为了研究IL-12和IGIF/ il -18在体内的作用,我们检测了感染麻风分枝杆菌的易感和耐药小鼠的细胞因子谱、细菌生长以及细胞因子治疗的潜在益处。感染后3 ~ 72 h,耐药小鼠接种部位IL-12 p40和IGIF/IL-18均有早期表达,而易感小鼠无。两株小鼠均未显示IFN-γ和IL-4的表达。IL-12给药可显著减少小鼠的细菌计数。lepraeinfection。结果表明,易感小鼠表现出1型辅助性T (Th1)反应的表达降低,而Th2反应没有相应的增加,并对外源性IL-12表现出应答性。IL-12治疗可能是治疗多发性硬化症的基本原理。lepraeinfection。
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