Interleukin-1β induces a reversible cardiomyopathy in the mouse

Abstract

Inflammatory mediators play a key role in the development and progression of heart failure. Interleukin-1β (IL-1β) is a prototypical inflammatory cytokine that suppresses myocyte contractility following acute administration. Healthy mice were randomly assigned to daily intraperitoneal injections of recombinant murine IL-1β (3 μg/kg in 0.2 ml) or matching volumes of NaCl 0.9 % solution (vehicle) for 15 days. Echocardiography was performed at baseline and 4 h (acute), followed by repeat measurements immediately prior to IL-1β or saline injections on days 5, 10, and 15 (chronic). Final echocardiography was performed on day 20 (5 days after last treatment). A subgroup of animals underwent isoproterenol challenge to evaluate contractile reserve at baseline, 4 h (acute), 15 days (chronic) and 20 days (recovery). IL-1β reduced left ventricular fractional shortening (LVFS) at 4 h versus vehicle (-24 vs. 0 %, respectively, P < 0.05). This reduction was maintained throughout chronic dosing at day 15. IL-1β-treated mice also showed impaired contractile reserve with a right shift of the dose-response curve to isoproterenol (P < 0.05) at 4 h and 15 days. By day 20, 5 days after stopping IL-1β, LVFS and contractile reserve had returned to baseline. IL-1β induces a reversible contractile dysfunction associated with impaired response to β-receptor stimulation.