Chronic beta-adrenergic activation-induced left ventricular systolic dysfunction is associated with systemic release of TNF-alpha and IL-1-beta in rats.

The relationship between systemic cytokine release and chronic beta-adrenergic activation-induced left ventricular dysfunction (LVSD) has not been widely reported in the literature. In the present study,we examined changes in the serum levels of inflammatory cytokines (IL-1-beta, IL-6 and TNF-alpha) following chronic beta-adrenergic activation-induced LVSD. Male Wistar rats were administered isoproterenol (ISO, 5 mg/kg, sc, once daily) for 4 weeks (ISO 4) or 12 weeks (ISO 12). Echocardiography was done and serum levels of IL-1-beta, IL-6 and TNF-alpha were estimated at the end of each protocol. In the ISO 4 group, there was a significant increase in relative wall thickness (p < 0.01) and heart weight: body weight ratio (p < 0.001) without any significant changes in fractional shortening (FS) or serum cytokine levels. However, in the ISO 12 group, there was a 32% decrease in FS along with increased serum levels of IL-1-beta and TNF-alpha. The present findings indicate that LVSD induced by chronic beta-adrenergic activation in rats is accompanied by increased serum cytokine levels.