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      The Study of Serum Level of Interleukin-2, Interleukin-6, and Tumor Necrosis Factor-alpha in Stable and Progressive Vitiligo Patients from Sina Hospital in Tabriz, Iran

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          Abstract

          Background:

          Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research have greatly supported the "Autoimmune theory." Vitiligo has two major forms: progressive and stable. As cytokines are important mediators of immunity, the most important of them are IL-2, IL-6, and tumor necrosis factor-α (TNF-α).

          Objectives:

          We aimed to study the serum level of IL-2, IL-6, and TNF-α in stable and progressive vitiligo and compared them to find a useful lab test to determine the form of vitiligo for diagnose and treatment.

          Materials and Methods:

          Serum IL-2, IL-6, and TNF-α were done by the indirect enzyme-linked immunosorbent assay (ELISA) in 40 cases of stable and progressive vitiligo.

          Results:

          Twenty patients had progressive vitiligo and 20 patients were stable vitiligo. In every group, there were seven male patients. Twenty-one patients had a positive family history of vitiligo and four patients had other autoimmune diseases. The average age and familial history between two groups and two genders were not meaningful. The mean serum TNF-α level was significantly higher in progressive than stable vitiligo. No significant difference was observed in the serum levels of IL-2, IL-6 between stable and progressive vitiligo. The mean serum IL-6 and TNF-α had higher levels in male patients.

          Conclusion:

          Analysis of TNF-α levels in every age or gender can show us the type of vitiligo, stable or progressive and we can choose the best form of treatment for patients.

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          Most cited references24

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          Evidence for an autoimmune pathogenesis of vitiligo.

          Vitiligo is a depigmenting disorder characterized by the development of white patches in various distributions, which are due to the loss of melanocytes from the epidermis. A variety of arguments from clinical observations to research findings in human and animal models support the hypothesis of autoimmunity and are reviewed in this article. The association with autoimmune diseases and organ-specific autoantibodies is well known. Various effective treatment options have an immunosuppressive effect. Today the autoimmune pathogenesis of the disease has become a rapidly evolving field of research. Detection of circulating melanocyte antibodies in human and animal models implicates a possible role of humoral immunity. Histological and immunohistochemical studies in perilesional skin suggest the involvement of cellular immunity in vitiligo. Recently, T-cell analyses in peripheral blood further support this hypothesis. Interestingly, new insights in the association of vitiligo and melanoma may help to clarify the role of autoimmunity in the development of vitiligo.
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            New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions.

            Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.
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              Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo.

              Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the important role of cellular autoimmunity in the pathogenesis of this disease. We isolated T cells from both perilesional and nonlesional skin biopsies obtained from five vitiligo patients, then cloned and analyzed their profile of cytokine production after short-term, nonspecific expansion in vitro. Perilesional T-cell clones (TCC) derived from patients with vitiligo exhibited a predominant Type-1-like cytokine secretion profile, whereas the degree of Type-1 polarization in uninvolved skin-derived TCC correlated with the process of microscopically observed melanocyte destruction in situ. Detailed analysis of broad spectrum of cytokines produced by perilesional- and nonlesional-derived CD4+ and CD8+ TCC confirmed polarization toward Type-1-like in both CD4 and CD8 compartments, which paralleled depigmentation process observed locally in the skin. Furthermore, CD8+ TCC derived from two patients also were analyzed for reactivity against autologous melanocytes. The antimelanocyte cytotoxic reactivity was observed among CD8+ TCC isolated from perilesional biopsies of two patients with vitiligo. Finally, in two of five patients, tetramer analysis revealed presence of high frequencies of Mart-1-specific CD8 T cells in T-cell lines derived from perilesional skin. Altogether our data support the role of cellular mechanisms playing a significant part in the destruction of melanocytes in human autoimmune vitiligo.
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                Author and article information

                Journal
                Indian J Dermatol
                Indian J Dermatol
                IJD
                Indian Journal of Dermatology
                Wolters Kluwer - Medknow (India )
                0019-5154
                1998-3611
                Jul-Aug 2021
                : 66
                : 4
                : 366-370
                Affiliations
                [1] From the Department of Dermatology, Faculty of Medicine, Tabriz University, Tabriz, Iran
                [1 ] Graduated from Pediatric, Faculty of Medicine, Tabriz University, Tabriz, Iran
                [2 ] Department of Immunology, Faculty of Medicine, Tabriz University, Tabriz, Iran
                Author notes
                Address for correspondence: Dr. Mehrdad Pashazadeh, Department of Immunology, Faculty of Medicine, Tabriz University, Tabriz, Iran. E-mail: mehrdad_pashazadeh@ 123456yahoo.com
                Article
                IJD-66-366
                10.4103/ijd.IJD_300_20
                8530078
                34759394
                a579dde1-5e50-425b-b23b-f191d9be41ef
                Copyright: © 2021 Indian Journal of Dermatology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : April 2020
                : May 2021
                Categories
                Original Article

                Dermatology
                cytokines,il-2,il-6,tnf-alpha,vitiligo
                Dermatology
                cytokines, il-2, il-6, tnf-alpha, vitiligo

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