Captopril prevents experimental autoimmune myocarditis.
Captopril, an angiotensin-converting enzyme inhibitor, is widely used in the treatment of a variety of cardiomyopathies, but its effect on autoimmune myocarditis has not been addressed experimentally. We investigated the effect of captopril on myosin-induced experimental autoimmune myocarditis. A/J mice, immunized with syngeneic cardiac myosin, were given 75 mg/L of captopril in their drinking water. Captopril dramatically reduced the incidence and severity of myocarditis, which was accompanied by a reduction in heart weight to body weight ratio and heart weight. Captopril specifically interfered with cell-mediated immunity as myosin delayed-type hypersensitivity (DTH) was reduced, while anti-myosin Ab production was not affected. Captopril-treated, OVA-immunized mice also exhibited a decrease in OVA DTH. In myosin-immunized, untreated mice, injection of captopril directly into the test site also suppressed myosin DTH. Interestingly, captopril did not directly affect Ag-specific T cell responsiveness because neither in vivo nor in vitro captopril treatment affected the proliferation, IFN-gamma secretion, or IL-2 secretion by Ag-stimulated cultured splenocytes. These results indicate that captopril ameliorates experimental autoimmune myocarditis and may act, at least in part, by interfering with the recruitment of cells to sites of inflammation and the local inflammatory environment.
Godsel
Lisa M
LM
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Leon
Juan S
JS
Wang
Kegiang
K
Fornek
Jamie L
JL
Molteni
Agostino
A
Engman
David M
DM
D000284:Administration, Oral; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D002216:Captopril / Q000008:administration & dosage* / Q000494:pharmacology; D006332:Cardiomegaly / Q000503:physiopathology / Q000517:prevention & control; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009205:Myocarditis / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009218:Myosins / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010047:Ovalbumin; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D009218:Myosins