This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fairweather, D. Articles by Rose, N. R. Search for Related Content PubMed PubMed Citation Articles by Fairweather, D. Articles by Rose, N. R.

(American Journal of Pathology. 2004;165:1883-1894.)
© 2004 American Society for Investigative Pathology

Interferon- Protects against Chronic Viral Myocarditis by Reducing Mast Cell Degranulation, Fibrosis, and the Profibrotic Cytokines Transforming Growth Factor-ß₁, Interleukin-1ß, and Interleukin-4 in the Heart

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

From the Departments of Pathology^* and Anesthesiology and Critical Care Medicine, and the W. Harry Feinstone Department of Molecular Microbiology and Immunology, the Johns Hopkins Medical Institutions, Baltimore, Maryland

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)-, are believed to exacerbate autoimmune diseases including myocarditis. In this study, we examined the effect of IL-12Rß1 and IFN- 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-ß₁, IL-1ß, and IL-4 in the hearts of IFN--deficient mice. All mice infected with CB3 developed DCM, but IFN--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-12Rß1 deficiency did not significantly alter the development of chronic myocarditis. Thus, IFN- 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-ß₁, IL-1ß, and IL-4 in the heart.

This article has been cited by other articles:

				D. Cihakova, J. G. Barin, M. Afanasyeva, M. Kimura, D. Fairweather, M. Berg, M. V. Talor, G. C. Baldeviano, S. Frisancho, K. Gabrielson, et al. Interleukin-13 Protects Against Experimental Autoimmune Myocarditis by Regulating Macrophage Differentiation Am. J. Pathol., May 1, 2008; 172(5): 1195 - 1208. [Abstract] [Full Text] [PDF]

				N. Grabie, I. Gotsman, R. DaCosta, H. Pang, G. Stavrakis, M. J. Butte, M. E. Keir, G. J. Freeman, A. H. Sharpe, and A. H. Lichtman Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8+ T-Cell-Mediated Injury in the Heart Circulation, October 30, 2007; 116(18): 2062 - 2071. [Abstract] [Full Text] [PDF]

				K. Reifenberg, H.-A. Lehr, M. Torzewski, G. Steige, E. Wiese, I. Kupper, C. Becker, S. Ott, P. Nusser, K.-I. Yamamura, et al. Interferon-{gamma} Induces Chronic Active Myocarditis and Cardiomyopathy in Transgenic Mice Am. J. Pathol., August 1, 2007; 171(2): 463 - 472. [Abstract] [Full Text] [PDF]

				L. S. Redwine, P. J. Mills, S. Hong, T. Rutledge, V. Reis, A. Maisel, and M. R. Irwin Cardiac-related Hospitalization and/or Death Associated With Immune Dysregulation and Symptoms of Depression in Heart Failure Patients Psychosom Med, January 1, 2007; 69(1): 23 - 29. [Abstract] [Full Text] [PDF]

				G. Szalay, M. Sauter, J. Hald, A. Weinzierl, R. Kandolf, and K. Klingel Sustained Nitric Oxide Synthesis Contributes to Immunopathology in Ongoing Myocarditis Attributable to Interleukin-10 Disorders Am. J. Pathol., December 1, 2006; 169(6): 2085 - 2093. [Abstract] [Full Text] [PDF]

				M. W. Cunningham T Regulatory Cells: Sentinels Against Autoimmune Heart Disease Circ. Res., November 10, 2006; 99(10): 1024 - 1026. [Full Text] [PDF]

				H. Mahrholdt, A. Wagner, C. C. Deluigi, E. Kispert, S. Hager, G. Meinhardt, H. Vogelsberg, P. Fritz, J. Dippon, C. -T. Bock, et al. Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis Circulation, October 10, 2006; 114(15): 1581 - 1590. [Abstract] [Full Text] [PDF]

				S. Frisancho-Kiss, J. F. Nyland, S. E. Davis, M. A. Barrett, S. J. L. Gatewood, D. B. Njoku, D. Cihakova, E. K. Silbergeld, N. R. Rose, and D. Fairweather Cutting Edge: T Cell Ig Mucin-3 Reduces Inflammatory Heart Disease by Increasing CTLA-4 during Innate Immunity. J. Immunol., June 1, 2006; 176(11): 6411 - 6415. [Abstract] [Full Text] [PDF]

				D. Fairweather, S. Frisancho-Kiss, D. B. Njoku, J. F. Nyland, Z. Kaya, S. A. Yusung, S. E. Davis, J. A. Frisancho, M. A. Barrett, and N. R. Rose Complement Receptor 1 and 2 Deficiency Increases Coxsackievirus B3-Induced Myocarditis, Dilated Cardiomyopathy, and Heart Failure by Increasing Macrophages, IL-1beta, and Immune Complex Deposition in the Heart J. Immunol., March 15, 2006; 176(6): 3516 - 3524. [Abstract] [Full Text] [PDF]

				D Fairweather and N R Rose Inflammatory heart disease: a role for cytokines Lupus, September 1, 2005; 14(9): 646 - 651. [Abstract] [PDF]

				M. Gharaee-Kermani, K. Hatano, Y. Nozaki, and S. H. Phan Gender-Based Differences in Bleomycin-Induced Pulmonary Fibrosis Am. J. Pathol., June 1, 2005; 166(6): 1593 - 1606. [Abstract] [Full Text] [PDF]