Immunoglobulin treatment ameliorates myocardial injury in experimental autoimmune myocarditis associated with suppression of reactive oxygen species.

[Aims]We tested the hypothesis that immunoglobulin ameliorated experimental autoimmune myocarditis (EAM) in mice attributing to the suppression of reactive oxygen species (ROS)-mediated myocardial injury. [Methods]We intraperitoneally administered intact type of human immunoglobulin (Ig) or F(ab′)2 fragments of human immunoglobulin, 1 g/kg/day daily for 3 weeks, to male BALB/c mice with heart failure due to EAM. [Results]The results showed that intact type of Ig, but not F(ab′)2 type, reduced the severity of myocarditis by comparing the heart weight/body weight and lung weight/body weight ratios, pericardial effusion score, macroscopic and microscopic scores. Tissue superoxide production was marked in untreated mice with EAM, which was suppressed by the treatment of immunoglobulins. The cytotoxic activities of lymphocytes in mice with EAM treated with Ig were reduced compared with untreated controls. The shift from Th1 toward Th2 cytokine balance was demonstrated by the treatment of immunoglobulins both in vitro and in vivo. [Conclusion]ROS may be involved in the development of myocarditis. Intact Ig ameliorates myocardial damage in mice with myocarditis associated with suppression of ROS and cytotoxic activity of lymphocytes

l-arginine ameliorates experimental autoimmune myocarditis by maintaining extracellular matrix and reducing cytotoxic activity of lymphocytes

It was previously shown that administration of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) aggravated murine viral myocarditis by increasing myocardial virus titres. Experimental autoimmune myocarditis in mice and rats mimics human fulminant myocarditis. The effects of l-arginine, a precursor of nitric oxide, upon heart failure in experimental autoimmune myocarditis were evaluated. Dietary l-arginine (l-arginine group) and l-arginine plus NG-nitro-l-arginine methyl ester (l-arginine + l-NAME group) were administered to C57BL/6 mice immunized with porcine cardiac myosin over 3 weeks. An untreated myocarditis group was prepared. Cardiac damage was less in the l-arginine group compared with the other two groups, as was incidence of heart failure. In addition, extracellular matrix change was less prominent in the l-arginine group. Plasma concentrations of nitric oxide were elevated in the l-arginine group. Cytotoxic activities of lymphocytes were lower in l-arginine group than in other two groups. l-arginine treatment may be effective in preventing the development of heart failure in experimental myocarditis by maintaining extracellular matrix and reducing the cytotoxic activity of lymphocytes