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Volunteers living in an area where schistosomiasis mansoni is endemic were subjected to ultrasound examination and classified into groups according to the levels of fibrosis diagnosed, namely, absence of indications of fibrosis (group 0), incipient fibrosis (group 1), and moderate/severe fibrosis (group 2). Peripheral blood mononuclear cells (PBMC) collected from the volunteers were stimulated with soluble antigens from adult schistosomes or from schistosome eggs, and the production of the cytokines gamma interferon, tumor necrosis factor alpha, transforming growth factor ␤ (TGF-␤), interleukin-4 (IL-4), IL-10, and IL-13 was determined. Potential associations of the level of fibrosis with age, sex, intensity of infection, and cytokine production were investigated between the three groups. Univariate analysis identified associations of age (>50), gender (male), and absence of eggs/g of feces with moderate/severe fibrosis and an association of intensity of infection (>100 eggs) with incipient fibrosis. When cytokine production in PBMC cultures stimulated by soluble egg antigens was categorized as low or high, significant differences in the distribution of IL-13 levels were established between groups 0 and 2. No significant differences were detected between the groups in the cytokines produced by PBMC cultures stimulated with soluble antigens from adult schistosomes. When all variables were tested in multivariate analyses, only IL-13 was strongly associated with fibrosis (odds ratio ‫؍‬ 5.8; 95% confidence interval [CI] ‫؍‬ 1

The role of cytokines on the in vitro proliferative response of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected patients to soluble egg (SEA) and adult worm antigens (SWAP) were evaluated. The results obtained demonstrated that the proliferative response of PBMC from chronic intestinal (INT) patients to SEA and SWAP is increased by the blockage of IL-10 with specific monoclonal antibodies (MAb). The effects of these antibodies were readily reversed by the addition of recombinant IL-10. In contrast, no effect was observed on the PBMC response of acute and hepatosplenic patients (HS) in the presence of anti-IL-10. Anti-IL-4 antibodies decreased the PBMC response of the intestinal (INT) and HS individuals to SEA and SWAP, and the PBMC response of acute patients to SEA but not to SWAP. Addition of anti-IL-5 MAb did not decrease the PBMC response of acute patients to SEA or SWAP. These results suggested that IL-10 has an important role in the modulation of the immune response in chronic asymptomatic patients and that this cytokine may be an important factor in controlling morbidity.

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals naturally resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results 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 cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-γ in the supernatants showed that PBMC from INT patients secreted low levels of IFN-γ upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-γ. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-γ may be associated with resistance to infection.

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