Intracellular Growth ofTrypanosoma cruziin Cardiac Myocytes Is Inhibited by Cytokine-Induced Nitric Oxide Release

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Abstract
The effect of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) onTrypanosoma cruzimultiplication and nitric oxide (NO) production in cardiac myocytes was investigated. Cardiac myocyte cultures were obtained from neonatal Wistar rat hearts, infected withT. cruzi, and treated with IL-1β, TNF-α, IFN-γ, orN-monomethyl-l-arginine (l-NAME) for 72 h. Parasite growth was calculated from the number of infected cells in Giemsa-stained smears. Nitric oxide production was determined with the Griess reagent. Inducible nitric oxide synthase (iNOS) expression by cardiac myocytes was detected by Western blot. The results showed that the percentages of cardiac myocytes containingT. cruziamastigotes in cytokine-treated cultures were significantly lower than in nontreated cultures. The addition ofl-NAME reversed the inhibitory effect on parasite growth of IL-1β and TNF-α but not of IFN-γ. Nitrite levels released byT. cruzi-infected and noninfected cardiac myocyte cultures after 72 h of stimulation with IL-1β were significantly higher than those produced upon treatment with TNF-α, IFN-γ, or medium alone, regardless of the infection status. Nitrite levels in TNF-α-stimulated infected cultures were significantly higher than in untreated infected cultures and TNF-α-treated noninfected cultures.l-NAME inhibited IL-1β- but not TNF-α-induced NO production, indicating the presence of iNOS-dependent and iNOS-independent mechanisms for NO formation in this experimental system. iNOS expression was detected in infected and noninfected cardiac myocytes stimulated with IL-1 β and TNF-α but not with IFN-γ. These results suggest an important role for cardiac myocytes and locally secreted cytokines in the control of parasite multiplication inT. cruzi-induced myocarditis.

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