Schistosoma japonicum egg granuloma formation in the interleukin-4 or interferon-gamma deficient host

The roles of interleukin (IL)-4 and interferon (IFN)-gamma in Schistosoma j aponicum egg granuloma formation were investigated in cercariae-infected (i nfection model) or after implantation of laid parasite eggs (egg implantati on model) in cytokine deficient mice. Two weeks after hepatic egg-implantat ion, a markedly decreased mononuclear cell infiltration and lack of multinu clear cell formation were characteristic features in IL-4 deficient mice. B y 4 weeks (late stage), the cellular reactions around the eggs were negligi ble in the deficient mice. Compared to the controls, there was a drastic re duction in the production of the Th2 cytokines, IL-4, IL-5 and IL-13. MCP-1 levels were also significantly lowered. in mice experimentally infected wi th cercariae, granuloma cellularity in both the wild-type and IL-4 deficien t mice at 45 days and 10 weeks postinfection was analogous to the egg impla ntation model at 2 and 4 weeks. Overall, the effects of IFN-gamma deficienc y on granuloma indiction differed markedly from the IL-4 results. Two weeks after egg implantation, IFN-gamma deficient mice showed suppressed neutrop hil response and hepatic necrosis with confluent mononuclear cell infiltrat ion along the outer layer of granulomas. By 4 weeks, there was a decrease i n cell infiltration, fibrosis and MCP-1 production while IL-10 production i ncreased. While these early characteristic features for IFN-gamma deficienc y were common to both the egg implantation (at 2 and 4 weeks) and cercariae infection model (at 45days), there was a surprising difference, i.e. marke d fibrosis was found in the late stages (ar 10 weeks postinfection) of cerc ariae-infected mice, but not in parasite egg implanted mice. Furthermore, w hile IL-13 levels were unchanged, both MCP-1 and IL-4 production were signi ficantly lower at 10 weeks in comparison with wild-type. The present study clearly demonstrates the importance of both Th1 and Th2 cytokine responses in S. japonicum egg-induced granuloma formation.