Key result
Antigenic stimulation with MAC in SIV-infected monkeys caused significant LVEF decline (19±2%) and LVEDD increase (26±6%), which was prevented by the TNFα antagonist etanercept.
Why the study?
Does TNFalpha antagonism with etanercept prevent the development of cardiomyopathy in a simian model of HIV infection subjected to antigenic stimulation?
Does TNFalpha antagonism with etanercept prevent the development of cardiomyopathy in a simian model of HIV infection subjected to antigenic stimulation?
Antigenic stimulation in a simian model of HIV infection induces TNFalpha-dependent dilated cardiomyopathy, which can be prevented by etanercept.
Etanercept prevented cardiomyopathy in this SIV model; leaves open TNFα antagonism for HIV cardiomyopathy in humans.
OBJECTIVE: To investigate a role for endogenous myocardial cytokine production in the development of HIV-associated cardiomyopathy. DESIGN: Cardiomyopathy is a late-stage sequela of HIV infection. Although pathogenesis of this condition in HIV infection is poorly defined, inflammatory cytokines are recognized for their detrimental effects on myocardial structure and function. HIV infection is characterized by chronic immune activation and inflammatory cytokine dysregulation. As the myocardium itself is a rich potential source of inflammatory cytokines, HIV-mediated cytokine dysregulation may be an important contributor to development of HIV cardiomyopathy. An antigenic stimulation protocol conducted in the simian immunodeficiency virus (SIV) model of HIV infection was used to study the effects of endogenous cytokine production on myocardial structure and function. METHODS: Twenty-six rhesus monkeys were assigned to treatment groups for a 35-day study. Animals were SIV-infected; SIV-infected and treated with killed Mycobacterium avium complex bacteria (MAC); SIV-infected, MAC-treated, and given the TNFalpha antagonist etanercept; or uninfected and MAC-treated. All animals were subjected to weekly echocardiographic studies. Hearts were collected for further evaluation at euthanasia. RESULTS: SIV-infected, MAC-treated animals developed significant systolic dysfunction [left ventricular ejection fraction (LVEF) decline of 19 +/- 2%] and ventricular chamber dilatation [left ventricular end-diastolic diameter (LVEDD) increase of 26 +/- 6%] not seen in other groups. Concurrent treatment with etanercept prevented development of these changes, implicating a causative role of myocardial TNFalpha. CONCLUSIONS: SIV-infected animals develop exaggerated myocardial pathology on stimulation with the ubiquitous environmental agent MAC. These responses are TNFalpha-dependent and may play a significant role in the development of cardiomyopathy in HIV infection.
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Yearley et al. (2008) studied HIV-associated cardiomyopathy (n=26). Mycobacterium avium complex bacteria (MAC) with or without etanercept vs. SIV-infected alone, or uninfected and MAC-treated was evaluated on Systolic dysfunction (LVEF decline) and ventricular chamber dilatation (LVEDD increase). Antigenic stimulation with MAC in SIV-infected monkeys caused significant LVEF decline (19±2%) and LVEDD increase (26±6%), which was prevented by the TNFα antagonist etanercept.
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