Impaired balance of interleukin-4 and interferon-gamma production in infections with Schistosoma mansoni and intestinal nematodes

Abstract

In chronic infection with Schistosoma mansoni, IL-4 and IFN-gamma are co-modulated in opposite directions. This was shown when testing sera and cell culture supernatants from 31 Brazilian patients with schistosomiasis before, and three months after treatment with praziquantel. Thorough examinations were undertaken to account for polyparasitism with intestinal nematode infections involving tissue migrating larval stages that may induce analogous changes. Controls free of S. mansoni included a group (n = 17) matching the schistosomiasis patients' parasitation by intestinal nematodes and a group (n = 16) free of helminths other than T. trichiura. Serum IL-4 was greater than 20 pg/ml in 81% of schistosomiasis patients but in only 35 and 25%, respectively, of controls with and without intestinal nematodes. IL-4 data correlated inversely with the mitogen-induced IFN-gamma synthesis. Generation of IL-4 in response to phorbol esters was related to the intensity of infection by schistosomes and intestinal nematodes. The parasitological status three months after therapy with either praziquantel or mebendazole revealed a dichotomy: whereas the ratio of IFN-gamma to IL-4 generated in vitro was identical in uninfected controls and in patients who cleared the parasites, failure to eliminate the parasites was associated with lower IFN-gamma/IL-4 ratios generated in vitro.