Regulatory role of interleukin-10 and interferon-γ in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum

Background. Schistosoma japonicum is the most pathogenic agent of hepatosplenic schistosomiasis. It causes fibrosis of the central (CentF) and peripheral (PerF) portal areas. We investigated whether CentF and PerF in Chinese fishermen infected with S. japonicum were associated with an abnormal production of cytokines and chemokines that, in experimental models, have been implicated in the regulation of fibrosis. Methods. Cytokines were measured by enzyme-linked immunosorbent assay in cultures of peripheral blood mononuclear cells from 127 patients, after stimulation with S. japonicum egg antigens. Data were analyzed by logistic regression that included age, sex, number of treatment episodes, alcohol use, and exposure as covariates. Results. CentF was associated with low levels of interleukin (IL)-10 (P = .0004), regulated on activation normally T cell expressed and secreted (P = .0004), and macrophage inflammatory protein-1 alpha (P = .007). In a multivariate analysis, only IL-10 was associated with CentF (odds ratio [OR], 10.8; 95% confidence interval [CI], 3.2-38; P = .0004). Splenomegaly was also associated with low IL-10 production and, independently, with CentF. In multivariate analysis, PerF was associated with low production of interferon (IFN)-gamma (OR, 8.2; 95% CI, 2-33; P = .0035) but not with production of IL-10. Conclusions. IL-10 is associated with protection against central fibrosis, because of its anti-inflammatory and antifibrosis effects. IFN-gamma is associated with protection against PerF, which depends more on egg load and egg-associated toxicity.