The contribution of interleukin (IL)-10 and interferon (IFN)-gamma to the regulation of type 1 and type 2 cytokine responses was investigated in Brazilians with different clinical forms of schistosomiasis mansoni. Cells from members of a family with acute intestinal schistosomiasis responded to schistosomal soluble egg antigen (SEA) or soluble adult worm antigen preparation (SWAP) with greater amounts of IFN-gamma than did cells from several patients with chronic intestinal schistosomiasis; IL-10 levels were similar. Neutralization of IL-10 had no effect on the SEA-specific IFN-gamma response in patients with acute infection, whereas SWAP-induced IFN-gamma was increased in both groups. Anti-IL-10 also up-regulated SEA-specific IFN-gamma protein and mRNA responses in most splenocyte cultures from hepatosplenic schistosomiasis patients but had no effect on antigen-specific IL-4 or IL-5 production. Neutralization of IFN-gamma resulted in a comparable increase in SWAP-specific IL-10 and IL-5, while IL-4 was not affected. These studies demonstrate that early disease in schistosomiasis is associated with a significant IFN-gamma response and that IL-10 contributes to the suppression of that response during both early and chronic infection.

Human infection with the parasite Loa loa is characterized by a good adaptation between the parasite and its host. One portion of the human population harbors only adult worms in subcutaneous tissues, whereas another portion also harbors the L1 microfilarial stage in peripheral circulation. This study was undertaken to understand the mechanisms by which the parasite evades or modulates host immunological attack. The cellular responses, based on T-cell proliferation, to the production of various cytokines (interleukin-2 [IL-2], gamma interferon [IFN-gamma], IL-4, and IL-5) and to expression of cytokine (IL-2, IFN-gamma, IL-4, IL-5, IL-10, and IL-12) mRNAs were investigated during the experimental infection with human parasite L. loa of a nonhuman primate which has been shown to display a spectrum of disease similar to that found in humans. Our results indicate that a T-cell unresponsiveness occurs when female worm products are released into the peripheral circulation, preceded by a transient period of strong T-cell proliferation, cytokine production, and cytokine mRNA expression. In the unresponsive state, only IL-10 mRNA is expressed, suggesting a role for IL-10 in down-regulation and maintenance of unresponsiveness. Taken together, these results indicate that both IL-10 production, which is known to inhibit B7 expression on monocytes, and the massive release of female products in the blood where T cells encounter antigens presented by nonactivated B lymphocytes, which lack costimulatory signals, should contribute to the inactivation of T cells.