Document Type : Original Article (s)
Authors
1
PhD Student of Immunology, Department of Microbiology, School of Veterinary Medicine, Urmia University, Urmia, Iran
2
Assistant Professor, Department of Microbiology, School of Veterinary Medicine, Urmia University, Urmia, Iran
3
Associate Professor, Department of Pathobiology, School of Veterinary Medicine, Urmia University, Urmia, Iran
4
Associate Professor, Department of Immunology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
Abstract
Background: Recent studies have demonstrated an important role for Th-17 and FoxP3+Treg lymphocytes in pathogenesis of autoimmune diseases. Although previous studies have demonstrated the immunomodulatory potential of statins (such as atorvastatin), these effects have been mostly justified by alterations in Th1/Th2 cytokines. The present study was carried out to investigate the therapeutic effects of atorvastatin on experimental autoimmune encephalomyelitis (EAE) and its effects on the response of T-helper cells. Methods: EAE was induced by MOG35-55 peptide and complete Freund's adjuvant in female C57BL/6 mice. The mice were placed in two therapeutic groups of 7. Treatment with atorvastatin (10 mg/kg daily) was started in the treatment group at day 12 when they developed a disability score. At the same time, the control group received vehicle alone with the same schedule. Signs of disease were recorded daily until the day 33 when mice were sacrificed. Then, splenocytes were tested to assess proliferation rate, cytokine, and the frequency of FoxP3+Treg cells by the 3-(4,5 dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assay (ELISA), and flow cytometry, respectively. Findings: Atorvastatin significantly decreased the clinical signs of established EAE. Aside from reducing lymphocyte proliferation, atorvastatin significantly inhibited the production of pro-inflammatory interleukin 17 (IL-17) as well as interferon gammas (IFN-γ) through antigen-specific restimulation. In addition, the level of anti-inflammatory IL-10 was significantly increased. However, the frequency of FoxP3+Treg cells did not alter significantly. Conclusion: Parallel with decreasing proliferation of autoreactive lymphocyte and cytokine production in favor of pro-inflammatory cytokines, atorvastatin ameliorated established EAE. Keywords: Experimental autoimmune encephalomyelitis, Atorvastatin, Lymphocyte response
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