Cytokine Production in Acute versus Chronic Human Schistosomiasis Mansoni: The Cross‐Regulatory Role of Interferon‐γ and Interleukin‐10 in the Responses of Peripheral Blood Mononuclear Cells and Splenocytes to Parasite Antigens

Abstract

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.

Cytokine profile associated with chronic and acute human schistosomiasis mansoni

“…The whole blood cultures were stimulated as previously described (Montenegro et al 1999). Parasite antigens, mitogens, antibodies and recombinant cytokines were added to the appropriate wells.…”

“…Cytokine level determination -The levels of IFN-γ and IL-4 were measured by enzyme linked immunosorbent assay (ELISA) using specific capture and detection monoclonal antibodies as previously described (Montenegro et al 1999). IL-13 production was measured using Quantikine Human IL-13 Immunoassay (R & D systems), following the manufacturer's instructions.…”

“…Mwatha et al (1998) associated high levels of TNF-α and IFN-γ and low levels of IL-5 with the presence of hepatosplenomegaly. Similarly, Montenegro et al (1999) demonstrated that there was marked production of IFN-γ, but not of IL-4 and IL-5 by parasite antigen-stimulated splenocytes from S. mansoni patients with HS disease. This study showed the contribution of IL-10 in the suppression of a significant IFN-γ response in the early and chronic phases of the disease.…”

“…Previous studies have shown that the pattern of cytokine production changes at different stages of human schistosomiasis. Moreover, it was more specifically demonstrated that early infection is associated with a significant IFN-γ response and IL-10 plays an important downregulatory role in that response during late infection (Montenegro et al 1999). The disease is more severe when the immunopathological mechanisms are dominant or effective control of the parasite is not attained (Chensue et al 1997).…”

Experimental models of Schistosoma mansoni infection

“…However idiotypes from mice without portal fibrosis stimulated IFN-γ formation (Montesano et al 1997). Clinical hepatosplenic disease in humans was associated with a Th1-type immunological response (Mwantha et al 1998) but Montenegro et al (1999) saw IFN-γ production in such patients only after neutralization of IL-10. Mice with and without pipestem hepatic fibrosis did not show differences in the production of anti-idiotypic antibodies against S. mansoni .…”