CYTOKINES AS DETERMINANTS OF RESISTANCE AND PATHOLOGY IN HUMAN SCHISTOSOMA-MANSONI INFECTION

The role of different cytokines in the peripheral blood mononuclear ce ll(PBMC) proliferative response and in in vitro granuloma formation wa s evaluated in a cross-sectional study with patients with the differen t clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals ''naturally'' resistant to infection named n ormal endemic (NE), The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative resp onse to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT ), chronic intestinal (INT) and hepatosplenic (HS) patients, Similar r esults were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS, In contrast, the addition of anti-IL-10 antibodies to PBMC cultur es from INT patients significantly increased the proliferative respons e to SEA and SWAP as well as the in vitro granuloma formation. Interes tingly, association of anti-IL-4 and anti-IL-10 antibodies did not inc rease the PBMC proliferative response of these patients, suggesting th at IL-10 may act by modulating IL-4 and IL-5 secretion, Addition of re combinant IL-10 decreased the proliferative response to undetectable l evels when PBMC from patients with the different clinical forms were u sed, Analysis of IFN-gamma in the supernatants showed that PBMC from I NT patients secreted low levels of IFN-gamma upon antigenic stimulatio n, In contrast, PBMC from NE secreted high levels of IFN-gamma. These data suggest that IL-10 is an important cytokine in regulating the imm une response and possibly controlling morbidity in human schistosomias is mansoni, and that the production of IFN-gamma may be associated wit h resistance to infection.