A cyclooxygenase-2 inhibitor alters Th1/Th2 cytokine balance and suppresses autoimmune myocarditis in rats.
Acute myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. Cyclooxygenase (COX)-2 is a key factor for progression of inflammation. Although inflammation is an essential pathological feature of acute myocarditis, the role of COX-2 in this process remains unclear. Thus, the purpose of this study was to clarify the role of COX-2 in acute myocarditis. We used a rat experimental autoimmune myocarditis (EAM) model and a specific COX-2 inhibitor in this study. Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. We administered the COX-2 inhibitor (meloxicam, 0.1 mg/kg per day) daily; the rats were killed on day 21. Echocardiograms, body and heart weight, heart rate, blood pressure, and histological and molecular examinations were performed. Cytokine expression in the hearts and cell proliferation against cardiac myosin were also analyzed. The COX-2 inhibition during the immune response (late) phase attenuated EAM development; however, the inhibition during the antigen priming (early) phase did not attenuate EAM. The COX-2 inhibitor altered Th1/Th2 cytokine balance and inhibited cell proliferation in vitro. The COX-2 inhibitor suppresses the development of EAM. COX-2 regulation is promising for treating acute myocarditis.
Suzuki
Jun-Ichi
J
Department of Cardiovascular Medicine, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Bunkyo, Japan. jsuzuki.cvm@tmd.ac.jp
Ogawa
Masahito
M
Futamatsu
Hideki
H
Kosuge
Hisanori
H
Tanaka
Hiroyuki
H
Isobe
Mitsuaki
M
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000473:pathology; D024722:Cardiac Myosins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D009205:Myocarditis / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D051546:Cyclooxygenase 2; D024722:Cardiac Myosins