(Circulation. 2001;103:18.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Lethal Autoimmune Myocarditis in Interferon-
Receptor–Deficient Mice
Enhanced Disease Severity by Impaired Inducible Nitric Oxide Synthase Induction
From Medicine A (F.F., U.W.), the Department of Pathology (M.O.K., P.S.), and the Division of Clinical Immunology, Department of Medicine (H.P.E.), University Hospital, Zurich, Switzerland, and the Medical Intensive Care Unit, University Hospital, Basel, Switzerland (U.E., R.B., S.M.).
Correspondence to Urs Eriksson, MD, Medical ICU, University Hospital, Petersgraben 5, CH-4031 Basel, Switzerland. klinerr@usz.unizh.ch.
Background—Interferon-
(IFN-) is an essential cytokine in the regulation of inflammatory
responses in autoimmune diseases. Little is known about its role in
inflammatory heart disease.
Methods and Results—We
showed that IFN- receptor–deficient mice
(IFN-R–/–) on a BALB/c
background immunized with a peptide derived from cardiac 
-myosin
heavy chain develop severe myocarditis with high mortality. Although
myocarditis subsided in wild-type mice after 3 weeks,
IFN-R–/– mice showed persistent
disease. The persistent inflammation was accompanied by vigorous in
vitro CD4 T-cell responses and impaired inducible nitric oxide synthase
expression, together with evidence of impaired nitric oxide production
in IFN-R–/– hearts. Treatment of
wild-type mice with the nitric oxide synthetase inhibitor
N-nitro-l-arginine-methyl-ester
enhanced in vitro CD4 T-cell proliferation and prevented healing of
myocarditis.
Conclusions—Our data
provide evidence that IFN- protects mice from lethal autoimmune
myocarditis by inducing the expression of inducible nitric oxide
synthase followed by the downregulation of T-cell
responses.
Key Words: interferons • mice • autoimmunity • myocarditis • myosin • nitric oxide synthase
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