Protective effects of losartan in mice with chronic viral myocarditis induced by coxsackievirus B3

Aim: To investigate whether losartan has protective effects in mice with chronic viral myocarditis induced by coxsackievirus B3 (CVB3). Main methods: Thirty two male Balb/c mice were intraperitoneally injected with CVB3 (10 x TCID50) to induce chronic viral myocarditis (CVM). Losartan at 12.5 mg/kg (n = 16) or normal saline (n = 16) were orally administered daily for 28 days to these mice. Uninfected mice (n = 6) were used as controls. On day 29, all mice underwent anesthesia and echocardiography prior to sacrifice. Serum IL-17, IL-4, IFN-gamma and TNF-alpha levels were measured by enzyme-linked immunosorbent assay, and cardiac tissues were histologically examined after hematoxylin & eosin staining. In addition, the effect of losartan on the virus titers in primary cultured neonatal rat cardiomyocytes infected with CVB3 was measured on Hep-2 cells at 72 h post infection. Key findings: Mice infected with CBV3 had significantly increased mortality, heart/body weight ratios, necrosis and inflammatory scores and decreased cardiac ejection fractions, compared with the controls (all P < 0.05). Losartan significantly decreased mortality from 40.0% to 12.5%, heart/body weight ratios from 7.08 +/- 2.17 to 4.15 +/- 0.99, and necrosis and inflammatory scores from 3.33 +/- 0.50 to 2.50 +/- 0.65 (all P < 0.05), and increased ejection fractions from 55.80 +/- 9.25 to 72.31 +/- 12.15 (P < 0.05). Losartan significantly enhanced IL-4, and decreased IFN-gamma, TNF-alpha and IL-17 (all P < 0.05). In the in vitro experiment, losartan had no influence on virus titers. Significance: Losartan protects mice against CVB3-induced CVM, most likely through upregulating Th2 responses, and down-regulating Th1 and Th17 responses. (C) 2013 Elsevier Inc. All rights reserved.