Daily administration of IL-18 for 7 days in healthy mice caused myocardial dysfunction, including a 40% reduction in the left ventricular maximal positive derivative (P<0.05).
Does chronic IL-18 exposure cause myocardial dysfunction in healthy mice and isolated cardiomyocytes?
Chronic administration of IL-18 induces left ventricular myocardial dysfunction, hypertrophy, and blunted beta-adrenergic responsiveness in healthy mice, suggesting a role in myocardial remodeling.
Effect estimate: 40% reduction
p-value: p=< 0.05
Although increased levels of circulating interleukin (IL)-18 have been demonstrated in patients with cardiovascular diseases, the functional consequences of chronically increased circulating IL-18 with respect to myocardial function have not been defined. Thus we aimed to examine the effects of chronic IL-18 exposure on left ventricular (LV) function in healthy mice. Moreover, to clarify whether IL-18 has direct effects on the cardiomyocyte, we examined effects of IL-18 on cardiomyocytes in vitro. After 7 days of daily intraperitoneal injections of 0.5 microg IL-18 in healthy mice, a 40% (P < 0.05) reduction in the LV maximal positive derivative, a 25% (P < 0.05) reduction in the LV maximal rate of pressure decay, and a 2.8-fold (P < 0.001) increase in the LV end-diastolic pressure were measured, consistent with myocardial dysfunction. Furthermore, we measured a 75% (P < 0.05) reduction in beta-adrenergic responsiveness to isoproterenol. IL-18 induced myocardial hypertrophy, and there was a 2.9-fold increase (P < 0.05) in atrial natriuretic peptide mRNA expression in the LV myocardium. In vitro examinations of isolated adult rat cardiomyocytes being stimulated with IL-18 (0.1 microg/ml) exhibited an increase in peak Ca2+ transients (P < 0.05) and in diastolic Ca2+ concentrations (P < 0.05). In conclusion, this study shows that daily administration of IL-18 in healthy mice causes LV myocardial dysfunction and blunted beta-adrenergic responsiveness to isoproterenol. A direct effect of IL-18 on the cardiomyocyte in vitro was demonstrated, suggesting that IL-18 reduces the responsiveness of the myofilaments to Ca2+. Finally, induction of myocardial hypertrophy by IL-18 indicates a role for this cytokine in myocardial remodeling.
Woldbæk et al. (Sat,) conducted a other in Healthy mice and isolated adult rat cardiomyocytes. Interleukin-18 (IL-18) was evaluated on Left ventricular maximal positive derivative (40% reduction, p=< 0.05). Daily administration of IL-18 for 7 days in healthy mice caused myocardial dysfunction, including a 40% reduction in the left ventricular maximal positive derivative (P<0.05).