title: Administration of granulocyte colony-stimulating factor induces immunomodulation, recruitment of T regulatory cells, reduction of myocarditis and decrease of parasite load in a mouse model of chronic Chagas disease cardiomyopathy.
abstract: Chagas disease, caused by Trypanosoma cruzi infection, is a leading cause of heart failure in Latin American countries. In a previous study, we showed beneficial effects of granulocyte colony-stimulating factor (G-CSF) administration in the heart function of mice with chronic T. cruzi infection. Presently, we investigated the mechanisms by which this cytokine exerts its beneficial effects. Mice chronically infected with T. cruzi were treated with human recombinant G-CSF (3 courses of 200 μg/kg/d for 5 d). Inflammation and fibrosis were reduced in the hearts of G-CSF-treated mice, compared with the hearts of vehicle-treated mice, which correlated with decreased syndecan-4, intercellular adhesion molecule-1, and galectin-3 expressions. Marked reductions in interferon-γ and tumor necrosis factor-α and increased interleukin-10 and transforming growth factor-β were found after G-CSF administration. Because the therapy did not induce a Th1 to Th2 immune response deviation, we investigated the role of regulatory T (Treg) cells. A significant increase in CD3(+)Foxp3(+) cells was observed in the hearts of G-CSF-treated mice. In addition, a reduction of parasitism was observed after G-CSF treatment. Our results indicate a role of Treg cells in the immunosuppression induced by G-CSF treatment and reinforces its potential therapeutic use for patients with Chagas disease.
authors: 1Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, Brazil 40296-710. milena@bahia.fiocruz.br.
authors: Juliana F
authors: JF
authors: Vasconcelos
authors: Bruno S F
authors: BS
authors: Souza
authors: Thayse F S
authors: TF
authors: Lins
authors: Letícia M S
authors: LM
authors: Garcia
authors: Carla M
authors: CM
authors: Kaneto
authors: Geraldo P
authors: GP
authors: Sampaio
authors: Adriano C
authors: AC
authors: de Alcântara
authors: Cássio S
authors: CS
authors: Meira
authors: Simone G
authors: SG
authors: Macambira
authors: Ricardo
authors: R
authors: Ribeiro-dos-Santos
authors: Milena B P
authors: MB
authors: Soares
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D006321:Heart / Q000469:parasitology; D006801:Humans; D056747:Immunomodulation; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000188:drug therapy*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D059208:Parasite Load; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037502:Galectin 3; D053671:Syndecan-4; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor
keywords: Th1 modulation; Trypanosoma cruzi; cytokine therapy; fibrosis; inflammation