IFN-gamma in human Chagas' disease: protection or pathology?

An apparently paradoxical role for IFN-gamma 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 bendnidazole during the acute phase of Trypanosoma cruzi infection and 2) chronically infected untreated patients. In the treated group, higher levels of IFN-gamma 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-gamma were produced by PBMC from cardiac patients in comparison with asymptomatic (indeterminate) patients. This apparently paradoxical role for IFN-gamma in human Chagas'disease is discussed in terms of the possibility of a temporal difference in IFN-gamma 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-gamma production during the chronic phase of the infection may favor cure or influence the development of the cardiac form of the disease.

Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection

The role of diferent 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 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 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-gamma in the supernatants showed that PBMC from INT patients secreted low levels of IFN-gamma upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-gamma. 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-gamma may be associated with resistance to infection.

Validity of selected clinical signs and symptoms in diagnosis of Schistosoma mansoni infection

Foi examinada a sensibilidade, a especificidade e os valores preditivos positivos de alguns sinais e sintomas para o diagnostico presumivel da infeccao pelo Schistosoma mansoni em uma area edemica de Minas Gerais (Divino): 403 individuos (69 por cento dos habitantes com mais de 1 ano de idade) participaram da investigacao. Maior sensibilidade foi observada para sangue nas fezes (13 por cento). Especificidades acima de 90 por cento foram encontradas para sangue nas fezes, e para figado palpavel com consistencia normal ou aumentada nas linhas hemi-clavicular (LHC) e medio-esternal (LME). Os maiores valores preditivos positivos para a infeccao foram observados para figado palpavel com consistencia aumentada na LME (83 por cento) ou LHC (75 por cento) e presenca de sangue nas fezes (78 por cento); os menores valores foram para figado palpavel com consistencia normal na LME (48 por cento) e LHC (45 por cento). A presenca de figado palpavel sem especificacao da sua consistencia tem sido tradicionalmente utilizada como um indicador da infeccao em areas onde a malaria ou o Kalazar nao sao endemicos. Nossos resultados mostram que a probabilidade de individuos com sangue nas fezes ou com aumento da consistencia do figado apresentarem a infeccao e maior do que entre aqueles com figago palpavel mas com a consistencia normal.

A multivariate analysis of socio-demographic factors, water contact patterns and Schistosoma mansoni infection in an endemic area in Brazil

Foi examinada a existencia de associacao entre fatores socio-demograficos, padroes de contatos com a agua e a infeccao pelo Schistosoma mansoni em uma area endemica em Minas Gerais (Divino), com o objetivo de determinar medidas prioritarias para prevenir a infeccao; 506 individuos (87 por cento dos habitantes com mais de 1 ano de idade) participaram do estudo. Aqueles que apresentavam ovos (n=198) foram comparados aos que nao apresentavam ovos de S. mansoni nas fezes (n=308). As seguintes variaveis exploratorias foram consideradas: idade, sexo, cor, tratamento anterior com esquistossomicida, local de nascimento, qualidade da habitacao, origem da agua para o domicilio, distancia do domicilio em relacao ao corrego, frequencia e motivos de contatos com agua. As variaveis que apresentaram associacoes independentes com a infeccao foram: idade (10-19 e * 20 anos), contato com aguas para trabalho agricola, pesca e natacao ou banho (Odds relativas ajustadas = 5.0, 2.4, 3.2, 2.1 e 2.0, respectivamente). Estes resultados sugerem que medidas para prevenir a infeccao devem priorizar os contatos com aguas para o trabalho e o lazer nesta area endemica.

Immunoregulation in human Schistosomiasis by idiotypic interactions and lymphokine-mediated mechanisms

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.

Characterization of human heterophil hemolysins induced by Schistosoma mansoni infection.

Anticorpos heterofilos foram detectados nos soros de pacientes normais ou com esquistossomose mansoni cronica. Suas atividades hemoliticas dependem da integridade da via classica do sistema do complemento.Os anticorpos heterofilos dos pacientes esquistossomoticos apresentaram maior especificidade para antigenos de Schistosoma mansoni do que aqueles anticorpos detectados nos soros de pacientes normais. A atividade hemolitica do anticorpo nos soros normais podia ser destruida pelo aquecimento destes soros a 56oC durante 4 minutos. Por outro lado, cerca de 80% dos soros de pacientes esquistossomoticos eram parcial ou totalmente resistentes ao mesmo tratamento. As atividades dos anticorpos heterofilos foram eluidas atraves da filtracao em gel, em diferentes fracoes no primeiro pico