Viral myocarditis leading to cardiomyopathy: Do cytokines contribute to pathogenesis?

D. A. Neumann, J. R. Lane, G. S. Allen, A. Herskowitz, N. R. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiotropic virus infection of mice typically produces florid myocardial inflammation and, in certain strains, elicits a chronic postinfectious autoimmune myocarditis. In humans, myocarditis may progress into cardiomyopathy manifested by interstitial fibrosis and myocyte hypertrophy in the absence of myocardial inflammation. Because of their pleiotropic effects, cytokines may provide a common link between connective tissue changes, myocardial injury, and cardiac autoimmunity. To explore such possibilities, histopathological and serological studies were performed on virus-infected mice which were or were not subject to cytokine manipulation. Mice infected with low doses of encephalomyocarditis virus exhibited little myocardial inflammation although myocyte hypertrophy and reactive fibrosis were common. Profound ultrastructural changes in the interstitium were observed through much of the noninflamed myocardium. B10.A mice which are resistant to the development of postinfectious autoimmune myocarditis developed severe autoimmune myocarditis when infected with Coxsackie virus B3 (CB3) and treated with bacterial lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin 1 (IL-1). B10.A mice given CB3, LPS, TNF, or IL-1 alone did not develop myocarditis and there was no evidence of autoimmune recognition of the heart. When CB3-infected A/J mice, which typically develop autoimmune sequelae to the infection, were treated with an IL-1 receptor antagonist, myocordial injury was diminished and heart antibody activity was reduced. These results suggest that TNF, IL-1, and possibly other cytokines contribute to myocardial pathogenesis and the induction of heart-specific autoimmunity. Further studies may lead to the development of cytokine-based therapeutic approaches to treating myocarditis and cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalClinical Immunology and Immunopathology
Volume68
Issue number2
DOIs
StatePublished - Aug 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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