Mechanisms of IL-6 mediated early inflammation in cardiac regeneration of neonatal mice

Objective: Our aim was to delve into the roles of IL-6 mediated early inflammation in cardiac regeneration of neonatal mice. Methods: A mouse model of apical heart resection was established to compare cardiac regeneration, protein positive rates, and expression levels of IL-6 in cardiac tissues, serum levels of IL-6, TNF-alpha and IL-1 beta (inflammatory cytokines) in cardiac tissues in the early period (at 1 day and 3 days) after surgery. We also examined mRNA and protein expression, phosphorylation of IL-6, Akt, and Stat3 in cardiac tissues of the mice among the normal mice (the control group and the model group), IL-6 gene knockout mice (the IL-6 knockout group), and IL-6 knockout mice whose overexpressed IL-6 vectors were transfected (the IL-6 rescue group). Results: At 21 days, regeneration of cardiomyocytes was repaired among mice in the control group, model group, and the IL-6 rescue group while scar repairs were present among mice in IL-6 knockout group. When compared with mice in control group, those in the IL-6 knockout group decreased significantly but those in model group and the IL-6 rescue group increased remarkably with regards to IL-6 protein positive rates, contents of IL-6, TNF-alpha, and IL-1 beta in serum, mRNA and protein expression of IL-6, Akt and Stat3, and protein expression levels of p-Akt and p-Stat3 (all P<0.05). Conclusion: IL-6 induces proliferation of cardiomyocytes and promotes cardiac regeneration in mice by mediating early inflammation in the mice.