Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis.
OBJECTIVE
Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated.


BACKGROUND
The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated.


METHODS
Lewis rats were immunized with cardiac myosin in complete Freund's adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured.


RESULTS
The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups.


CONCLUSIONS
Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages.
Zhang
S
S
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Kodama
M
M
Hanawa
H
H
Izumi
T
T
Shibata
A
A
Masani
F
F
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D015726:Giant Cells / Q000187:drug effects / Q000276:immunology; D008297:Male; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009218:Myosins / Q000276:immunology; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D016896:Treatment Outcome
D000906:Antibodies; D016572:Cyclosporine; D011239:Prednisolone; D009218:Myosins; D001241:Aspirin