GSBS Student Publications

Title

Antigenic stimulation in the simian model of HIV infection yields dilated cardiomyopathy through effects of TNFalpha

UMMS Affiliation

Graduate School of Biomedical Sciences; University of Massachusetts

Date

3-5-2008

Document Type

Article

Medical Subject Headings

Animals; Antigens, Bacterial; Biological Markers; Cardiomyopathy, Dilated; Disease Models, Animal; Disease Progression; Immunoglobulin G; Immunohistochemistry; Immunosuppressive Agents; Interleukin-18; Macaca mulatta; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare; Infection; Myocardium; Nitric Oxide Synthase Type II; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Simian Acquired Immunodeficiency Syndrome; *Simian immunodeficiency virus; Tumor Necrosis Factor-alpha

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: AIDS. 2008 Mar 12;22(5):585-94. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

AIDS (London, England)

PubMed ID

18316999