title: [The protective role of interleukin-6 monoclonal antibody on experimental autoimmune myocarditis and its mechanism].
abstract: OBJECTIVE
  To investigate the therapeutic effect of IL-6 mAb on experimental autoimmune myocarditis (EAM) in rats, and search the mechanism of the role of IL-6, helper T cells 17 (Th17) and regulative T cells (Treg) in EAM pathogenesis.
  
  
  METHODS
  Thirty-four Lewis rats were divided into three groups randomly, i.e. control group (n = 6), EAM group (n = 12), and IL-6 mAb intervention group (n = 16). Rats in EAM group and IL-6 mAb intervention group were injected intracutaneously with myosin to establish EAM model. Rats in IL-6 mAb intervention group were injected intraperitoneally with 1 mg IL-6 mAb on 1st, 7th to 20th day after cardiac myosin immune injection. Myocardial inflammation was examined by HE stain, Masson stain, and TdT assay (TUNEL reaction) on 21st and 84th day after IL-6 mAb therapy in order to assess the therapeutic role. Spleen cells were analyzed by flow cytometry to illustrate Th17 and Treg cells? number and function. The serum concentration of IL-6, IL-10, IL-17, and TGF-beta in each group was measured by ELISA, concentration of STAT3, RORgammat, and Foxp3 mRNA in each group was determined with RT-PCR. Spleen cells derived from EAM were stimulated by IL-6 mAb in vitro, and the concentration of IL-10, IL-17 and TGF-beta was measured by ELISA.
  
  
  RESULTS
  Inflammation score, fibrosis score, and apoptosis index in IL-6 mAb intervention group were significantly decreased as compared with those in EAM group (P < 0.01). The number of Th17 and Treg cells in EAM group on the 21st day (experimental acute peak stage) were increased, and those in intervention group on the 21st day were significantly inhibited (P < 0.01). The concentration of serum IL-6, IL-10, IL-17 and TGF-beta in intervention group on the 21st day was decreased dramatically in comparison with that in EAM group on the same day (P < 0.01). The levels of peripheral blood STAT3, RORgammat, Foxp3 mRNA in intervention group on the 21st day was decreased significantly as compared with that in EAM group (P < 0.01). The expression of IL-10, IL-17 and TGF-beta was increased significantly (P < 0.01) by stimulation of IL-6 mAb on spleen cells derived from EAM in vitro.
  
  
  CONCLUSIONS
  IL-6 mAb could neutralize IL-6, and ameliorate myocarditis and reduce heart autoimmune responses. IL-6 mAb has significantly protective effects on EAM by suppressing Th17 and Treg cells.
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Han
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Wang
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Guo-Lei
authors.initials: GL
authors.lastname: Ding
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; C515934:Il17a protein, rat; D020381:Interleukin-17; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10