Crucial Role of Interleukin-6 in the Development of Norepinephrine-induced Left Ventricular Remodeling in Mice

Abstract

Background: Elevated serum concentration of interleukin (IL)-6 is a predictor for poor prognosis in congestive heart failure. It was shown previously in rats, that IL-6 expression in the left ventricle (LV) was followed by LV hypertrophy. Methods: Using IL-6 deficient mice (IL-6^-/-), we studied the role of IL-6 in a model of norepinephrine (NE)-induced LV hypertrophy. Results: In wild type (WT) mice, IL-6 mRNA expression and its concentration in the serum were elevated after 4 h of NE-treatment (s.c. 0.25 mg/kg·h). Further, NE-induced LV hypertrophy was detected: LV weight/body weight (LVW/BW) ratio (+12.3±3%, p < 0.05) and mRNA expression of atrial natriuretic peptide (ANP) in WT mice (+120±25%, p < 0.05) after 3 days were increased. In contrast, NE did not induce elevation of LVW/BW ratio and ANP expression in IL-6^-/- mice. Replacement with recombinant IL-6 restored the hypertrophy-inducing effect of NE in IL-6^-/- mice. As to the extracellular matrix (ECM) proteins, NE increased collagen type I and III expression only in WT mice and not in IL-6^-/- mice. The addition of recombinant IL-6 elevated the expression of the ECM proteins to the WT level. Conclusion: IL-6 is a major player in the development of NE-induced LV hypertrophy in mice.