title: Role for interleukin-1 beta in Trypanosoma cruzi-induced cardiomyocyte hypertrophy.
abstract: Chagas' disease, the leading cause of heart failure in Latin America, results from infection with the intracellular protozoan parasite Trypanosoma cruzi. Host cell responses elicited in the myocardium early in the infective process are thought to be critical for establishment of infection by this pathogen; however, these changes have not been well characterized. We report here that primary cardiomyocytes undergo hypertrophy as an early response to T. cruzi infection. The T. cruzi-elicited hypertrophic response is characterized by increased expression of genes encoding the contractile proteins MyHC beta and MyHC alpha, followed by an approximately twofold increase in cell size. Hypertrophy was observed in both parasite-containing and noninfected cell populations represented in T. cruzi-infected cultures, indicating the involvement of a soluble mediator in this process. Conditioned medium harvested from T. cruzi-infected cultures, which contained significant levels of interleukin-1 beta (IL-1 beta) but not endothelin-1 or tumor necrosis factor alpha, was sufficient to induce hypertrophy in isolated cardiomyocytes. Addition of a high-affinity receptor chimera, IL-1 trap, to cardiomyocyte cultures blocked the overall increase in cell size elicited by T. cruzi. These novel findings indicate that IL-1 beta, which is rapidly induced in response to T. cruzi, promotes cardiomyocyte hypertrophy early in the infective process and may contribute to maintenance of cardiomyocyte function during establishment of T. cruzi infection in the heart.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Petersen
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Burleigh
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology / Q000276:immunology / Q000473:pathology; D048429:Cell Size; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000209:etiology* / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D051381:Rats; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
chemical_list: D007375:Interleukin-1