Effect Of Gene Delivery Of Plasmid Encoding Interleukin-1Receptor Ⅱ For Treatment Of Rat Autoimmune Myocarditis

AIM: To evaluate the effect of gene delivery of plasmid encoding IL-1RⅡ fortreatment of rat experimental autoimmune myocarditis (EAM) and elucidate an aspectof the biological activities of IL-1RⅡ. Methods: Cardiac myosin was emulsified withan equal volume of Complete Freund’s adjuvant and EAM models were produced byinjection with the preparation in both footpads of Lewis rats. Rats were immunized onday0and were injected with plasmid encoding IL-1RⅡ by hydrodynamics-basedgene delivery on day6. The expression of IL-1RⅡ on day7, day12, day17wasdetermined by Western blot. Echocardiography was performed on day16and ratswere sacrificed on day17. The effect of IL-1RⅡ gene therapy was evaluated by theratio of heart weight/body weight, histopathological scores, relative expression ofbrain natriuretic peptide (BNP) in hearts and echocardiographic parameters. Theexpression of IL-1related cytokines, including IL-1β, prostaglandin E2synthase(PGEs) and Monocyte chemotactic protein1(MCP-1), were also detected.Results: After hydrodynamics-based gene delivery on day6, the expression ofIL-1RⅡ on day7increased until to day17. Rats in the control group showedsignificantly myocardial damage and a decreased of the left ventricular function.Rats in the treatment group injected with IL-1RⅡ plasmid showed an improvement ofcardiac function. The ratio of heart weight/body weight, histopathological scores,level of BNP were significantly lower in treatment group than the control group. Thelevel of IL-1β,PGEs and MCP-1mRNA and protein expression were alsosignificantly inhibited in the IL-1RⅡ treatment group. Conclusions:Hydrodynamics-based gene delivery encoding IL-1RⅡ plasmid effectively preventedthe progression of the LV remodeling and myocardial damage in rat experimentalautoimmune myocarditis.