Details

Autor(en) / Beteiligte

• FAIRWEATHER, Delisa
• FRISANCHO-KISS, Sylvia
• YUSUNG, Susy A
• BARRETT, Masheka A
• DAVIS, Sarah E
• GATEWOOD, Shannon J. L
• NIOKU, Dolores B
• ROSE, Noel R

Titel

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

Ist Teil von

• The American journal of pathology, 2004-12, Vol.165 (6), p.1883-1894

Ort / Verlag

Bethesda, MD: American Society for Investigative Pathology

Erscheinungsjahr

2004

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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 IL-12Rβ1 and IFN-γ 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-β 1 , 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-β 1 , IL-1β, and IL-4 in the heart.