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

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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.