Erythromycin treatment suppresses myocardial injury in autoimmune myocarditis in rats via suppression of superoxide production.
BACKGROUND
Recent evidence suggests that erythromycin (EM), a major macrolide antibiotic, has many biological functions in addition to the anti-bacterial actions, including anti-inflammatory and free radical scavenging actions. However, the effects of the drug upon inflammatory myocardial diseases are unknown. We tested the hypothesis that EM ameliorates experimental autoimmune myocarditis in rats attributing to the suppression of superoxide production.


METHODS
We administered EM, 3.3mg/kg/day and 33 mg/kg/day, intraperitoneally for 3 weeks, to rats with experimental autoimmune myocarditis (EAM) produced by immunization by porcine myosin.


RESULTS
EM treatment reduced the severity of myocarditis compared with the untreated group in a dose-dependent manner by comparing the heart weight/body weight ratio, pathologic scores, and myocardial macrophage, CD4(+), and CD8(+) infiltrations. Echocardiographic study showed that increased left ventricular posterior wall thickness produced by myocardial inflammation was reduced by EM treatment. Myocardial superoxide production, determined by dihydroethidium staining, was significantly reduced by the treatment. Western blotting showed that the expression of myocardial interleukin-1β was reduced by EM treatment compared with untreated groups. The in vivo dorsal air pouch model showed that EM significantly suppressed leukocyte chemotaxis in a dose-dependent manner.


CONCLUSIONS
Irrespective of a well-known classic antibiotic, EM attenuated EAM not only by the anti-inflammatory action but by the suppression of superoxide production.
Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Emi
E
Hirano
Kana
K
Shimada
Taeka
T
Komiyama
Masatoshi
M
Fujita
Chiharu
C
Kishimoto
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*; D004917:Erythromycin / Q000494:pharmacology / Q000627:therapeutic use*; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D016896:Treatment Outcome
D013481:Superoxides; D004917:Erythromycin