Functional analysis of interleukin-18 in Schistosma japonicum infection and granuloma formation

白细胞介素-18 （IL-18）最初是作为干扰素-g诱导因子被发现的，越来越多的报道表明它在各种传染病的保护中具有重要作用。然而，尚未有关于日本血吸虫感染和卵卵周围肉芽肿形成的报道，而肉芽肿是该病的主要发病机制。利用IL-18敲除（KO）小鼠，作者在肉芽肿形成、感染抗性和细胞因子调节方面发现了有趣的发现，并将结果与野生型、IL-4KO和IFN-γ KO小鼠进行了比较。一项关于IL-18产生的调查显示，在野生型和IL-4KO小鼠感染的血清中有显著的IL-18产生，但在IFN-γ KO小鼠中没有。细胞因子分析表明，在感染和卵植入模型中，IL-18KO小鼠都倾向于增强Th2细胞因子（IL-4、IL-13、IL-5）的反应，而IFN-γ的产生则减少，这些现象在植入后期（4周）尤为明显。鸡蛋植入模型的肉芽肿形成在第4周明显增加，与Th2细胞因子反应增强一致，而在第2周看到较小的肉芽肿。感染后，IL-18KO小鼠嗜酸性粒细胞染色下降，但原因尚不清楚。在感染抗性方面，IL-18KO小鼠在重复实验中令人惊讶地显示出较少的蠕虫恢复。总之，IL-18无疑影响日本血吸虫感染的细胞因子谱、肉芽肿形成和抗性。

Interleukin-18 (IL-18) was initially discovered as interferon-g inducing factor in P.acness infection and increasing reports have indicated the importance in the protection of various infectious diseases. However, no reports have been published for the roles of Schistosoma japonicum infection and granuloma formation around deposited eggs which is central pathogenesis of the disease. Using IL-18 knockout (KO) mice, author revealed interesting findings in granuloma formation, resistance to infection, and cytokine regulation and the results were assessed comparing with those in wild type, IL-4KO and IFN-γ KO mice. An investigation on IL-18 production showed a significant production in infected sera of wild type and IL-4KO mice, but not in IFN-γ KO mice. Cytokine analysis indicated that in both infection and egg-implanted model, IL-18KO mice tended to augment Th2 cytokine (IL-4, IL-13, IL-5) response, while IFN-γ production reduced and these phenomena were particularly seen at late stage (4 weeks) of implantation. Granuloma formation studied with egg-implanted model apparently increased at 4 weeks in coincidence with augmented Th2 cytokine response, while rather smaller granulomas were seen at 2 weeks. In infection, IL-18KO mice showed decreased stain for eosinophils, though the reason was not elucidated. Regarding infection resistance, IL-18KO mice surprisingly showed less worm recovery in repeated experiments. In conclusion, IL-18 undoubtedly affect on cytokine profile, granuloma formation and resistance in S.japonicum infection.