title: Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a Th1-specific immune response.
abstract: The role of interleukin 10 (IL-10) and gamma interferon (IFN-gamma) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-gamma, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-gamma producers. PBMC from IND patients classified as low IFN-gamma producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14(High+) cells), whereas in the CARD group, the major sources of IFN-gamma were T lymphocytes (CD3(+) CD4(+) cells). These results suggest an association between the production of IFN-gamma by CD3(+) CD4(+) cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-gamma against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
authors.forename: J A S
authors.initials: JA
authors.lastname: Gomes
authors.forename: L M G
authors.initials: LM
authors.lastname: Bahia-Oliveira
authors.forename: M O C
authors.initials: MO
authors.lastname: Rocha
authors.forename: O A
authors.initials: OA
authors.lastname: Martins-Filho
authors.forename: G
authors.initials: G
authors.lastname: Gazzinelli
authors.forename: R
authors.initials: R
authors.lastname: Correa-Oliveira
mesh_terms: D000328:Adult; D000368:Aged; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma