Local expression of interleukin-1 receptor antagonist by plasmid DNA improves mortality and decreases myocardial inflammation in experimental coxsackieviral myocarditis

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. A plasmid vector expressing hIL-1Ra (total 40 microg/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 10(4) 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