Schistosoma japonicum egg granuloma formation in the interleukin‐4 or interferon‐γ deficient host

The roles of interleukin (IL)‐4 and interferon (IFN)‐γ in Schistosoma japonicum egg granuloma formation were investigated in cercariae‐infected (infection model) or after implantation of laid parasite eggs (egg implantation model) in cytokine deficient mice. Two weeks after hepatic egg‐implantation, a markedly decreased mononuclear cell infiltration and lack of multinuclear cell formation were characteristic features in IL‐4 deficient mice. By 4 weeks (late stage), the cellular reactions around the eggs were negligible in the deficient mice. Compared to the controls, there was a drastic reduction 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 with cercariae, granuloma cellularity in both the wild‐type and IL‐4 deficient mice at 45 days and 10 weeks postinfection was analogous to the egg implantation model at 2 and 4 weeks. Overall, the effects of IFN‐γ deficiency on granuloma induction differed markedly from the IL‐4 results. Two weeks after egg implantation, IFN‐γ deficient mice showed suppressed neutrophil response and hepatic necrosis with confluent mononuclear cell infiltration along the outer layer of granulomas. By 4 weeks, there was a decrease in cell infiltration, fibrosis and MCP‐1 production while IL‐10 production increased. While these early characteristic features for IFN‐γ deficiency were common to both the egg implantation (at 2 and 4 weeks) and cercariae infection model (at 45 days), there was a surprising difference, i.e. marked fibrosis was found in the late stages (at 10 weeks postinfection) of cercariae‐infected mice, but not in parasite egg implanted mice. Furthermore, while IL‐13 levels were unchanged, both MCP‐1 and IL‐4 production were significantly 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.