title: Immunoregulatory actions of melatonin and zinc during chronic Trypanosoma cruzi infection.
abstract: After one century of the discovery of Chagas' disease and the development of an efficient drug with amplitude of actions both in the acute and chronic phase is still a challenge. Alternative immune modulators have been exhaustively used. For that purpose, melatonin and zinc were administered during chronic Trypanosoma cruzi-infected Wistar rats and several endpoints were assessed. Melatonin has a remarkable functional versatility, being associated with important antioxidant, anti-inflammatory, and anti-apoptotic effects. The cross-talk between zinc and the immune system includes its ability to influence the production and signaling of numerous inflammatory cytokines in a variety of cell types. Our study showed that zinc triggered a decrease in the generation of IFN-γ for TCD4(+) cells. Reduced percentage of CD4(+) T cells producing TNF-α was observed in control melatonin or zinc-and-melatonin-treated animals as compared with untreated rats. On the other hand, a significant increase in the percentage of IL-4 from CD4(+) and CD8(+) T lymphocytes producers was observed 60 days after infection, for all zinc-treated animals, whether infected or not. Melatonin and zinc therapies increased the percentages of CD4(+) and CD8(+) T lymphocytes IL-10 producers. CD4(+) CD25(high) Foxp3(+) T cells were also elevated in zinc- and melatonin-treated animals. The modulation of the immune system influenced by these molecules affected cytokine production and the inflammatory process during chronic T. cruzi infection. Elucidation of the interplay between cytokine balance and the pathogenesis of Chagas' disease is extremely relevant not only for the comprehension of the immune mechanisms and clinical forms but, most importantly, also for the implementation of efficient and adequate therapies.
authors.affiliation: Laboratório de Parasitologia, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: Vânia
authors.initials: V
authors.lastname: Brazão
authors.forename: Fabricia Helena
authors.initials: FH
authors.lastname: Santello
authors.forename: Marina Del Vecchio
authors.initials: Mdel V
authors.lastname: Filipin
authors.forename: Angela Palamin
authors.initials: AP
authors.lastname: Azevedo
authors.forename: Míriam Paula Alonso
authors.initials: MP
authors.lastname: Toldo
authors.forename: Fabiana Rossetto
authors.initials: FR
authors.lastname: de Morais
authors.forename: José Clóvis
authors.initials: JC
authors.lastname: do Prado
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015032:Zinc / Q000627:therapeutic use*
chemical_list: D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D015032:Zinc; D008550:Melatonin
keywords: Trypanosoma cruzi; immune response; melatonin; zinc