Kawakami K, Koguchi Y, Qureshi M H, Kinjo Y, Yara S, Miyazato A, Kurimoto M, Takeda K, Akira S, Saito A
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan.
FEMS Microbiol Lett. 2000 May 1;186(1):121-6. doi: 10.1111/j.1574-6968.2000.tb09092.x.
Using interleukin (IL)-18 deficient (IL-18(-/-)) mice, we examined the role of IL-18 in the host resistance and Th1 response against infection with Cryptococcus neoformans. Fungal clearance in the lung was reduced in IL-18(-/-) mice, although there was no significant change in the level of dissemination to the brain. The DTH response, as determined by footpad swelling, was also diminished in IL-18(-/-) mice compared to control wild-type (WT) mice. The levels of IL-12 and interferon (IFN)-gamma in the sera were significantly lower in IL-18(-/-) mice than in WT mice. Spleen cells from infected WT mice produced a high level of IFN-gamma upon stimulation with the microbe, while only a low level of IFN-gamma production was detected in spleen cells from infected IL-18(-/-) mice. Administration of IL-18 almost completely restored the reduced response in IL-18(-/-) mice, while IL-12 showed a marginal effect. These results demonstrated the important role of IL-18 in the resistance and Th1 response of mice to C. neoformans by potentiating the production of IFN-gamma.
利用白细胞介素（IL）-18缺陷（IL-18(-/-)）小鼠，我们研究了IL-18在宿主抵抗新型隐球菌感染及Th1反应中的作用。尽管IL-18(-/-)小鼠向脑部扩散的水平没有显著变化，但肺部的真菌清除能力降低。与对照野生型（WT）小鼠相比，通过足垫肿胀测定的迟发型超敏反应（DTH）在IL-18(-/-)小鼠中也减弱。IL-18(-/-)小鼠血清中IL-12和干扰素（IFN）-γ的水平显著低于WT小鼠。感染的WT小鼠的脾细胞在受到微生物刺激后产生高水平的IFN-γ，而在感染的IL-18(-/-)小鼠的脾细胞中仅检测到低水平的IFN-γ产生。给予IL-18几乎完全恢复了IL-18(-/-)小鼠中降低的反应，而IL-12显示出轻微的作用。这些结果证明了IL-18通过增强IFN-γ的产生在小鼠对新型隐球菌的抵抗和Th1反应中的重要作用。
