title: Modulatory effect of celastrol on Th1/Th2 cytokines profile, TLR2 and CD3+ T-lymphocyte expression in a relapsing-remitting model of multiple sclerosis in rats.
abstract: Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of brain and spinal cord that has an increasing incidence worldwide and classically presents in a relapsing-remitting form. This study was designed to induce a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE) to investigate the possible modulatory effect of celastrol on Th1/Th2 cytokines profile, immunohistochemical expression of TLR2, and CD3+T-lymphocytic count. Eighteen female Sprague Dawley rats were divided into 3 groups; where group I served as normal control, group II as EAE+vehicle, and group III as EAE treated by celastrol (1mg/kg/day, i.p.) started at 10th day till 42nd day post-immunization. The clinical score of rats in group II (EAE+vehicle) was relapsed after the re-challenge at the 35th day post-immunization and exhibited significant positive association with serum TNF-α, NF-κB expression and nitrites levels in brain and spinal cord, and CD3+ T-lymphocytic count in brain tissues while serum IL-10 showed significant negative association. Treatment of EAE by celastrol caused amelioration of the clinical score and inhibited the relapse. It caused significant shift in cytokines profile from Th1 by decrease in TNF-α towards Th2 pattern by increase in IL-10. Moreover, celastrol treatment resulted in significant reduction in NF-κB expression, nitrites levels, as well as immunohistochemical expression of TLR2 and CD3+ T-lymphocytic count. The beneficial effect of celastrol was further confirmed histopathologically by reduction in H&E score. Collectively, these results provide a promising pre-clinical evidence and conclusion about use of celastrol in treatment of multiple sclerosis that must be accessed in further clinical studies.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tanta University, Al-Geish Street, Postal No. 31527, Egypt. Electronic address: amanyabdin@med.tanta.edu.eg.
authors.forename: Amany A
authors.initials: AA
authors.lastname: Abdin
authors.affiliation: Department of Pathology, Faculty of Medicine, Tanta University, Egypt.
authors.forename: Eiman A
authors.initials: EA
authors.lastname: Hasby
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000097:blood; D018655:Lymphocyte Count; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D029757:Tripterygium; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D007155:Immunologic Factors; D016328:NF-kappa B; D009573:Nitrites; D053978:Pentacyclic Triterpenes; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C050414:celastrol
keywords: CD3+ T-lymphocyte; Celastrol; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Th1/Th2 cytokines; Toll like receptors