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Induction of proinflammatory cytokine expression in experimental acute Chagasic cardiomyopathy
B Chandrasekar1, P C Melby, D A Troyer
1Department of Medicine, University of Texas Health Science Center, San Antonio, USA.
Insights
Chagas' disease (Trypanosoma cruzi) infection causes inflammation in the heart muscle. This study found that the infected heart tissue itself produces inflammatory cytokines, worsening cardiac pathology.
Area of Science:
- Immunology
- Cardiology
- Parasitology
Background:
- Chagas' disease, caused by Trypanosoma cruzi, is linked to progressive cardiomyopathy.
- Elevated serum TNF-alpha levels are associated with Chagas' disease, and TNF-alpha can impair cardiac function.
Purpose of the Study:
- To investigate whether pro-inflammatory cytokines are produced within the myocardium during Trypanosoma cruzi infection.
- To determine the role of myocardial cytokine production in Chagas' disease pathology.
Main Methods:
- Lewis rats were infected with Trypanosoma cruzi trypomastigotes.
- Histological analysis was performed to assess myocardial infection and inflammation.
- Northern and Western blot analyses were used to measure the expression of IL-1beta, TNF-alpha, and IL-6 mRNA and protein levels in heart tissue.
Main Results:
- Infected rat hearts showed significant myocyte infection with T. cruzi amastigotes and minimal inflammation.
- High levels of IL-1beta, TNF-alpha, and IL-6 gene expression were detected in infected hearts compared to controls.
- Protein levels of these cytokines were also elevated in infected hearts, correlating with mRNA levels.
Conclusions:
- Trypanosoma cruzi infection induces the production of pro-inflammatory cytokines directly within the myocardium.
- This endogenous cytokine production may contribute to the mechanical damage and adverse functional effects observed in Chagas' disease cardiomyopathy.
- Targeting myocardial cytokine production could be a therapeutic strategy for Chagas' disease.
Abstract:
One of the hallmarks of Chagas' disease (caused by Trypanosoma cruzi) is progressive cardiomyopathy. The disease is associated with increased serum TNF-alpha levels, and TNF-alpha is known to depress cardiac function. It is, however, not known whether the cytokines are produced within the infected myocardium. One-month-old male Lewis rats were injected with cell culture-derived T. cruzi trypomastigotes and killed 15 days post-infection. As compared to normal animals, histologic analysis of infected animals revealed dense infection with amastigotes within myocytes and a minimal inflammatory infiltrate in the myocardium. Northern blot analysis of total RNA revealed no signal for IL-1beta or TNF-alpha, and a weak signal for IL-6 in the control rat hearts, and high levels of expression for the three genes in the infected rats. Western blots revealed results similar to that of mRNA levels, suggesting that, in addition to mechanical damage, infection by T. cruzi induces proinflammatory cytokine production in the myocardium itself, which may further exacerbate the pathology, and affect adversely myocardial function.