The Therapeutic Role Of Interleukin-6Monoclonal Antibody In Experimental Autoimmune Myocarditis

Objective: This study investigated the inhibition effect of IL-6mAb on Experimentalautoimmunity myocarditis in rats, and discussed the pathological roles of IL-6in theregulation of Th17and Treg cells in EAM.Methods: Lewis rats were divided into three groups randomly: Normal control group,n=6, EAM experimental group, n=12, and IL-6mAb intervention group. According tothe different operation time, the EAM group and intervention group were divided intoacute inflammation (21day) and chronic duration (84day) group. EAM model wereinduced by myosin from porcine heart. Rats received IL-6mAb1mg intraperitonealinjection,1,7to20days after immune injection. Myocardial inflammation wereexamined by HE stain, Masson stain, and TdT-mediated dutp nick end labeling(TUNEL) method21and84days after medicine，The quantitative analysis of theTh17and Treg cells in spleen cells by flow cytometry. Stimulated EAM derivedspleen cells in vitro, and measured the concentration of IL-10, IL-17and TGF-β.Determination of the concentration of cytokins (IL-6, IL-10, IL-17, and TGF-β) inserum by ELISA. Concentration of STAT3, RORγt, and Foxp3mRNA tested withRT-PCR.Results: In the acute peak group of EAM, the IL-6mAb invention group wasdecreased significant than the EAM group in inflammation score, fibrosis score andapoptosis index(P<0.01).The number of Th17and Treg cells on experimental acute peak group (21d EAMgroup) increased, and21d intervention group was significantly inhibited (P<0.01). The concentration of serum IL-6, IL-10, IL-17and TGF-β on21d intervention groupdecreased dramatically than the21d experiment group(P<0.01), The mRNA level ofSTAT3, RORγt and Foxp3in peripheral blood was markedly different between IL-6mAb intervention group and EAM experimental group(P<0.01). In chronic persistentperiod of EAM, the STAT3and RORγt mRNA level increased, while the FoxP3mRNA level declined. Stimulation of IL-6mAb EAM source of spleen cells in vitro,IL-10, IL-17and TGF-β was inhibited (P<0.01).Conclusions:1. Neutralization of IL-6ameliorated myocarditis and reduced heart autoimmunityresponses.2. Th17, Treg cells participate in the process of EAM acute onset.3. In chronic persistent period of EAM, Th17mediated inflammation plays a majorrole, while Treg inhibited...