Cytokine production in acute versus chronic human schistosomiasis mansoni:The cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens

The contribution of interleukin (IL)-10 and interferon (IFN)-gamma to the r egulation of type 1 and type 2 cytokine responses was investigated in Brazi lians with different clinical forms of schistosomiasis mansoni. Cells from members of a family with acute intestinal schistosomiasis responded to schi stosomal soluble egg antigen (SEA) or soluble adult worm antigen preparatio n (SWAP) with greater amounts of IFN-gamma than did cells from several pati ents with chronic intestinal schistosomiasis; IL-10 levels were similar, Ne utralization of IL-10 had no effect on the SEA-specific IFN-gamma response in patients with acute infection, whereas SWAP-induced IFN-gamma was increa sed in both groups. Anti-IL-10 also up-regulated SEA-specific IFN-gamma pro tein and mRNA responses in most splenocyte cultures from hepatosplenic schi stosomiasis patients but had no effect on antigen-specific IL-4 or IL-5 pro duction. Neutralization of IFN-gamma resulted in a comparable increase in S WAP-specific IL-10 and IL-5, while IL-4 was not affected. These studies dem onstrate that early disease in schistosomiasis is associated with a signifi cant IFN-gamma response and that IL-10 contributes to the suppression of th at response during both early and chronic infection.