The effect of daily administration of IL-18 on cardiac structure and function

Abstract

Recently, the cytokine Interleukin-18 (IL-18) has been shown to be increased as a result of cardiac surgery. Elevated IL-18 has been associated with neurological dysfunction, systemic inflammatory response syndrome (SIRS), and multiple organ dysfunction syndrome (MODS) post open-heart surgery. The intent of the study contained herein was to determine the effect of IL-18 administration on cardiac function and structure. Eight C57BL/6 female mice were treated daily with 0.5μg/mouse of recombinant IL-18 for 7 days. Long axis echocardiography (ECHO) measurements of the anatomical and hemodynamic function of the heart for all mice were studied 24h after the last dose. The left ventricular wet weights increased from 84 ± 1 to 93 ± 3 mg when comparing the placebo (n = 8) with the IL-18 groups, respectively ( p = 0.01). With ECHO analysis, IL-18 significantly increased left ventricular (LV) mass, the left atrium dimensions (LA), and the left ventricular posterior wall thickness (LVPW) over the 8-day time period ( p < 0.01). There was a 5-fold increase in interstitial cardiac collagen content and a 30% increase in myocyte size in the IL-18 compared with the control groups ( p < 0.01). Administration of IL-18 appears to induce interstitial fibrosis and myocyte hypertrophy, resulting in increased ventricular stiffness. Thus, increased IL-18 during and post open-heart surgical procedures may induce left ventricular diastolic dysfunction and affect post-operative outcomes.