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(Circulation. 2002;105:1278.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Local Expression of Interleukin-1 Receptor Antagonist by Plasmid DNA Improves Mortality and Decreases Myocardial Inflammation in Experimental Coxsackieviral Myocarditis

Byung-Kwan Lim, MSc; Seong-Choon Choe, MD, PhD; Jae-Ok Shin, BSc; Seong-Hyun Ho, MSc; Jong-Mook Kim, PhD; Seung-Shin Yu, PhD; Sunyoung Kim, PhD; Eun-Seok Jeon, MD, PhD

From the Department of Medicine, Cardiovascular Institute, Samsung Medical Center (B.-K.L., J.-O.S., E.-S.J.); Medical Department, MSD Korea Ltd (S.-C.C.); ViroMed Limited, Technology Business Incubator (S.-H.H., J.-M.K., S.-S.Y); and Institute of Molecular Biology and Genetics (S.K.), Seoul National University, Seoul, South Korea..

Correspondence to Eun-Seok Jeon, MD, PhD, Department of Medicine, Cardiovascular Institute, Samsung Medical Center, 50 Ilwon-dong, Kangnam-ku, Seoul, 135-710, South Korea. E-mail esjeon1107{at}hanmail.net

Background— The inflammatory cytokines have an important role in the pathogenesis of viral myocarditis. Inerleukin-1 (IL-1) is one of the major cytokines that modulate the outcome of viral infection. Among the methods for in vivo gene transfer, direct injection of plasmid DNA is one that is simple and feasible. In this study, we expressed human IL-1 receptor antagonist (hIL-1Ra) in the mouse heart by direct injection of a novel plasmid vector and evaluated its effects on coxsackieviral (CVB3) myocarditis.

Methods and Results— A plasmid vector expressing hIL-1Ra (total 40 µg/mouse) was injected into the heart apex of 8-week-old inbred female Balb/C mice (day 3). On day 0, mice (IL-1Ra-CVB3, n=35) were infected intraperitoneally with 10⁴ PFU of CVB3; control mice (pCK-CVB3, n=15) were injected with empty vector on day -3 and infected on day 0. hIL-1Ra was expressed in the heart, reached its peak on day 5, and persisted for 2 weeks. The 14-day survival rate of IL-1Ra-CVB3 was higher (77%) than that of controls (30%, P<0.01). Myocardial virus titers on day 3 were lower in IL-1Ra-CVB3 mice. Myocardial inflammation on day 7 and fibrosis on day 14 were markedly decreased in IL-1Ra-CVB3.

Conclusion— These results showed that direct injection of the expression plasmid vector into the heart was an effective method to transfer the cytokine gene in vivo, and expressed IL-1Ra in the heart can modulate the deleterious effect of the host immune response in viral myocarditis.

Key Words: myocarditis • interleukin • gene therapy

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