Interferon-γ protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines transforming growth factor-β1, interleukin-1β, and interleukin-4 in the heart

De Lisa Fairweather, Sylvia Frisancho-Kiss, Susy A. Yusung, Masheka A. Barrett, Sarah E. Davis, Shannon J.L. Gatewood, Dolores B. Njoku, Noel R. Rose

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Inflammatory fibrosis is a characteristic feature of myocarditis, dilated cardiomyopathy (DCM), and congestive heart failure. Th1-type immune responses, mediated by interleukin (IL)-12-induced interferon (IFN)-γ, are believed to exacerbate autoimmune diseases including myocarditis. In this study, we examined the effect of DL-12Rβ1 and IFN-β deficiency on the development of chronic CB3-induced myocarditis using knockout mice. We found increased chronic CB3-induced myocarditis (14.1 to 43.1%, P < 0.001); pericarditis (1.5 to 7.6%, P < 0.001); fibrosis (9-7 to 27.4%, P < 0.05); and the profibrotic cytokines transforming growth factor-β1, IL-1β, and IL-4 in the hearts of IFN-γ-deficient mice. All mice infected with CB3 developed DCM, but IFN-γ-deficient mice developed a fibrous, adhesive pericarditis associated with increased numbers of degranulating mast cells (MCs) in the pericardium (26.6 to 45.9%, P < 0.01), increased histamine levels (716 to 1930 ng/g of heart, P < 0.01), and reduced survival (100 to 43%). In contrast, IL-12Rβ1 deficiency did not significantly alter the development of chronic myocarditis. Thus, IFN-γ protects against the development of severe chronic myocarditis, pericarditis, and DCM after CB3 infection by reducing MC degranulation, fibrosis, and the profibrotic cytokines transforming growth factor-β1, IL-1β, and IL-4 in the heart.

Original languageEnglish (US)
Pages (from-to)1883-1894
Number of pages12
JournalAmerican Journal of Pathology
Volume165
Issue number6
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Interferon-γ protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines transforming growth factor-β<sub>1</sub>, interleukin-1β, and interleukin-4 in the heart'. Together they form a unique fingerprint.

  • Cite this