Abstract
Purpose: Interleukin-1 (IL-1) is a powerful and important cytokine in myocarditis. The purpose of this study was to evaluate the effect and possible mechanism of hydrodynamics-based delivery of the IL-1 receptor antagonist (IL-1RA)-immunoglobulin (Ig) gene for treatment of rat autoimmune myocarditis (EAM). Method: On the day following immunization, rats were transfected with either pCAGGS encoding IL-1RA-Ig or with pCAGGS encoding Ig alone and on day 17 the extent of EAM was evaluated. Furthermore, we examined the expression of IL-1 related genes in purified cells from EAM hearts and the effect of serum containing IL-1RA-Ig for cultivated cells targeted by IL-1. Result: IL-1RA-Ig gene therapy was effective in controlling EAM, as monitored by decreased heart weight/body weight ratio, reduced myocarditis areas and gene expression of atrial natriuretic peptide in hearts. Examination of the expression of IL-1 related genes suggested that the target cells were mainly non-cardiomyocytic non-inflammatory cells and alpha beta T-cells. The expression of several immunologic molecules (prostaglandin E synthase, cyclooxygenase-2 and IL-1beta) in cultivated non-cardiomyocytic cells and Th1 cytokines (IL-2 and IFN-gamma) in cultivated lymphocytes was significantly decreased by the presence of IL-1RA-Ig in the serum. Conclusion: EAM was suppressed by hydrodynamics-based delivery of plasmid DNA encoding IL-1RA-Ig gene. IL-1RA-Ig suppressed gene expression of prostaglandin synthases and IL-1 in non-cardiomyocytic cells and Th1 cytokines in lymphocytes.
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