Abstract
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-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.
Highlights
Infection by Schistosoma mansoni (S. mansoni) in man induces multiple cellular and humoral immune responses to the parasite antigens that are believed to determine the outcome of the disease
These results can be interpreted as a lack of production of this cytokine by peripheral blood mononuclear cells (PBMC) from acute patients or inability of PBMC from these individuals to respond to IL-10
Flow cytometry analysis of the PBMC populations of patients in the acute phase of the disease demonstrated a significant increase in CD4+HLA-DR+ T cells as well as in CD3-CD2+ (NK) cells. These results suggest that significant cell activation occurs during the acute phase of the disease and that this activation may involve IFN-γ secretion by NK cells
Summary
R. Corrêa-Oliveira Laboratório de Imunologia Celular e Molecular Centro de Pesquisas René Rachou FIOCRUZ Avenida Augusto de Lima, 1715 30190-002 Belo Horizonte, MG Brasil Fax: 55 (013) 295-3115 Presented at the International Meeting on Cytokines, Angra dos Reis, RJ, Brasil, November 24-28, 1996. Research supported by the European Commission, INCO-DC Programme, NIH (No AI 26505), CNPq, FAPEMIG, FINEP-CNPq (PRONEX) and the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.
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