Lipoxin A4 mitigates experimental autoimmune myocarditis

Abstract. – OBJECTIVE: Myocarditis, an acute inflammation disease of the heart, is a potentially lethal disease and can lead to sudden death. This study aims to investigate the therapeutic effect of lipoxin A4 (LXA4) on experimental autoimmune myocarditis (EAM) and to explore the underlying mechanism. MATERIALS AND METHODS: EAM was induced in BALB/c mice by injection of porcine cardiac myosin and LAX4 at doses of 10 or 50 μg/kg was administrated from day 1 to 21. The severity of myocarditis was evaluated by detection of heart weight/body weight (HW/BW) ratio and histopathological examination of the heart. Cardiac function and heart structure were assessed by echocardiography. Serum levels of Th1 and Th2 cytokines were determined by ELISA. Protein expression was detected by Western blot analysis. RESULTS: The results demonstrated that LXA4 mitigated the severity of myocarditis by decreasing HW/BW ratio and reducing infiltration of inflammatory cells. Echocardiographic analysis indicated that cardiac function of LXA4-treated rats was significantly improved compared with non-treated group. LXA4 treatment significantly increased the levels of Th1 cytokines (TNF-α and IL-6) and decreased Th2 cytokines (IL-4 and IL-10). Furthermore, LXA4 administration effectively inhibited NF-κB nuclear translocation and deactivated PI3K/Akt pathway. CONCLUSIONS: LXA4 has a protective effect against EAM by reducing the inflammatory response and inhibiting NF-κB and PI3K/Akt signaling pathway. European Review for Medical and Pharmacological Sciences 2017; 21: 1850-1859