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      Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

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          Abstract

          Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.

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          Inflammatory bowel disease.

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            Cytokine pathways and joint inflammation in rheumatoid arthritis.

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              Increased expression of interleukin 17 in inflammatory bowel disease.

              Interleukin (IL) 17 is a cytokine which exerts strong proinflammatory activities. In this study we evaluated changes in IL-17 expression in the inflamed mucosa and in the serum of patients with inflammatory bowel disease (IBD). Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n=20), Crohn's disease (CD) (n=20), infectious colitis (n=5), ischaemic colitis (n=8), and normal colorectal tissues (n=15). IL-17 expression was evaluated by a standard immunohistochemical procedure. Serum IL-17 levels were determined by ELISA. IL-17 mRNA expression was analysed by reverse transcriptase-polymerase chain reaction. IL-17 expression was not detected in samples from normal colonic mucosa, infectious colitis, or ischaemic colitis. In the inflamed mucosa of active UC and CD patients, IL-17 expression was clearly detectable in CD3(+) T cells or CD68(+) monocytes/macrophages. The average number of IL-17(+) cells was significantly increased in active UC and CD patients compared with inactive patients. IL-17 mRNA expression was not detected in normal mucosa but was detectable in the mucosa from active UC and CD patients. IL-17 was not detected in the sera from normal individuals, infectious colitis, or ischaemic colitis patients but IL-17 levels were significantly elevated in IBD patients. IL-17 expression in the mucosa and serum was increased in IBD patients. It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                June 2013
                31 May 2013
                : 14
                : 6
                : 11742-11766
                Affiliations
                [1 ]Department of Biology and Anatomy, National Defense Medical Center, No. 161, Section 6, MinChuan East Road, Neihu, Taipei City 114, Taiwan; E-Mail: lingujiun@ 123456mail.ndmctsgh.edu.tw
                [2 ]Department of General Surgery, Tri-Service General Hospital, No.325, Section 2, Chenggong Rd., Neihu District, Taipei City 114, Taiwan; E-Mail: doc20333@ 123456yahoo.com.tw
                [3 ]Graduate Institute of Medical Sciences, National Defense Medical Center, No. 161, Section 6, MinChuan East Road, Neihu, Taipei City 114, Taiwan; E-Mails: pedneuchen@ 123456hotmail.com (S.-J.C.); chw@ 123456ms3.hinet.net (C.-H.W.)
                [4 ]Department of Pediatrics, Tri-Service General Hospital, No.325, Section 2, Chenggong Rd., Neihu District, Taipei City 114, Taiwan
                [5 ]Department of Otolaryngology—Head and Neck Surgery, Tri-Service General Hospital, No.325, Section 2, Chenggong Rd., Neihu District, Taipei City 114, Taiwan
                [6 ]Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, No. 161, Section 6, MinChuan East Road, Neihu, Taipei City 114, Taiwan
                [7 ]Department of Microbiology and Immunology, National Defense Medical Center, No. 161, Section 6, MinChuan East Road, Neihu, Taipei City 114, Taiwan
                [8 ]Rheumatology/Immunology/Allergy, Tri-Service General Hospital, No.325, Section 2, Chenggong Rd., Neihu District, Taipei City 114, Taiwan; E-Mail: ming0503@ 123456ms3.hinet.net
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: sytwu@ 123456ndmctsgh.edu.tw ; Tel.: +886-2-8792-3100 (ext. 18540); Fax: +886-2-8792-1774.
                Article
                ijms-14-11742
                10.3390/ijms140611742
                3709754
                23727938
                c745950f-37bd-4c72-8e69-60f6efa2c6e7
                © 2013 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 28 February 2013
                : 15 May 2013
                : 16 May 2013
                Categories
                Review

                Molecular biology
                melatonin,autoimmune disease,multiple sclerosis,systemic lupus erythematosus,rheumatoid arthritis,type 1 diabetes mellitus,inflammatory bowel disease

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