An apparently paradoxical role for IFN-<FONT FACE="Symbol">g</font> in human Chagas' disease was observed when studying the pattern of cytokine production by peripheral blood mononuclear cells (PBMC) obtained from two groups of chagasic patients after specific stimulation with Trypanosoma cruzi-derived antigens. The groups studied were 1) patients treated with benznidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-<FONT FACE="Symbol">g</font> were produced by PBMC from individuals cured after treatment when compared to non-cured patients. In contrast, in the chronically infected group (not treated) higher levels of IFN-<FONT FACE="Symbol">g</font> were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-<FONT FACE="Symbol">g</font> in human Chagas' disease is discussed in terms of the possibility of a temporal difference in IFN-<FONT FACE="Symbol">g</font> production during the initial stages of the infection (acute phase) in the presence or absence of chemotherapy. The maintenance of an immune response with high levels of IFN-<FONT FACE="Symbol">g</font> production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease

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-<FONT FACE="Symbol">g</font> in the supernatants showed that PBMC from INT patients secreted low levels of IFN-<FONT FACE="Symbol">g</font> upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-<FONT FACE="Symbol">g</font>. 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-<FONT FACE="Symbol">g</font> may be associated with resistance to infection.

Anti-idiotypic (anti-Id) T cells from schistosomiasis patients or former patients proliferate upon exposure to polyclonal or monoclonal anti-soluble egg antigen (SEA) antibodies. Chloroquine does not inhibit, the response, which is induced by F(ab')2 (but not soluble Fab) fragments of these antibodies. Purified T cells from former patients require macrophages or exogenous IL-1 to respond to anti-SEA Ids and can respond to matrix-bound Fab fragments in the presence of IL-1. These anti-Id T cells recognize the Ids directly. Chronic schistosomiasis patients immunoregulate the production of a non-IL-2 lymphokine that stimulates IL-2 receptor expression on resting T cells. This regulation is reversed upon chemotherapeutic cure.

Anticorpos heterófilos foram detectados nos soros de pacientes normais ou com esquistossomose mansoni crônica. Suas atividades hemolíticas dependem da integridade da via clássica do sistema do complemento. Os anticorpos heterófilos dos pacientes esquistossomóticos apresentaram maior especificidade para antígenos de Schistosoma mansoni do que aqueles anticorpos detectados nos soros de pacientes normais. A atividade hemolítica do anticorpo nos soros normais podia ser destruída pelo aquecimento destes soros a 56ºC durante 4 minutos. Por outro lado, cerca de 80% dos soros de pacientes esquistossomóticos eram parcial ou totalmente resistentes ao mesmo tratamento. As atividades dos anticorpos heterófilos foram eluídas através da filtração em gel, em diferentes frações no primeiro pico.

Heterophil antibodies could be detected in sera from normal or from patient with chronic schistosomiasis. Their hemolytic activities depend on the integrity of the complement classic pathway. The heterophil antibodies from patient sera presented a higher specificity for Schistosoma mansoni antigen preparations than those detected in normal sera. Most of the hemolytic activity observed in normal sera can be destroyed at 56ºC for 4 min. On the other hand, about 80% of the sera from infected patients are partially or totally resistant to this heat-treatment. The hemolytic activities of sera were eluted from a gel filtration column in different fractions of the first peak.