A nonsteroid anti-inflammatory drug exacerbates coxsackie B3 murine myocarditis

• Published in: Journal of the American College of Cardiology 1985-11, Vol.6 (5), p.1078-1082
• Main Authors: Costanzo-Nordin, Maria Rosa, Reap, Elizabeth A., O'connell, John B., Robinson, John A., Scanlon, Patrick J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiovascular system; Coxsackievirus Infections - drug therapy; Coxsackievirus Infections - pathology; Enterovirus B, Human; Ibuprofen - therapeutic use; Male; Medical sciences; Mice; Mice, Inbred BALB C; Miscellaneous; Myocarditis - drug therapy; Myocarditis - pathology; Myocardium - pathology; Necrosis; Pharmacology. Drug treatments
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(85)80312-0

Nonsteroid anti-inflammatory drugs are often used to treat myalgias and arthralgias in enteroviral infections, but their effects on acute viral myocarditis are unknown. The effect of the nonsteroidal anti-inflammatory drug, ibuprofen, on acute viral myocarditis was studied in 75 four week old male BALB/c mice infected with 1.75 × 107plaque-forming units of Coxsackie virus B3 on day 0. Ibuprofen was given intraperitoneally at a dose of 15 mg/kg body weight daily. The mice were assigned to four groups—Group I, 18 uninfected mice given ibuprofen on days 1 to 14; Group II, 18 infected, untreated mice; Group III, 20 infected mice given ibuprofen on days 1 to 14; and Group IV, 17 infected mice given ibuprofen on days 7 to 14. Nine animals in Group I, eight in Group II and seven in Group III were killed on day 7; the remaining mice were killed on day 14. Heart viral cultures and histologic analysis were done. Cultures at days 7 and 14 were all negative. Inflammation and necrosis analyzed in each animal were graded 0 to 4, with grade 4 representing widespread inflammation and necrosis. The heart was histologically normal in all 18 uninfected mice (Group I) given ibuprofen only. Inflammation and necrosis were not significantly different in Group II (infected, untreated) and Group III (infected, treated beginning day 1) mice killed at day 7. Inflammation scores of mice killed on day 14 were 2.1 ± 0.6 (Group H), 3.1 ± 0.7 (Group III) and 2.9 ± 1.0 (Group IV infected, treated days 7 to 14). Necrosis scores of mice killed on day 14 were 1.5 ± 0.8 (Group II), 3.0 ± 0.9 (Group III) and 2.7 ± 1.1 (Group IV). When compared with Group II (infected, but not treated), both inflammation and necrosis were significantly worse in Group III (p < 0.01) and Group IV (p < 0.05). These results indicate that ibuprofen worsens myocardial inflammation and necrosis during acute viral myocarditis. This effect, not attributable to viral persistence in the myocardium, may be related to immunomodulating properties of ibuprofen on prostaglandin-sensitive mononuclear cells.