Evaluation of Macrophage Inhibitory Factor (MIF) Level in Serum and Lesional Skin of Patients with Alopecia Areata

Abstract

Alopecia areata (AA) is a common dermatological problem that manifests as sudden loss of hair without any inflammation or scarring. The hair loss might be seen in a circumscribed area, in the whole scalp (alopecia totalis; AT) or in the whole body (alopecia universalis; AU). The course of disease is not predictable and it is often associated with periods of hair loss and re-growth. Although the complete picture for AA pathogenesis has yet to be determined, previous research has made much progress in the understanding of this disease mechanism. Numerous circumstantial evidences support the notion that AA is fundamentally a disease mediated by inflammatory cells and may be autoimmune in nature. Cellular immunity is known to have a role in the pathogenesis of alopecia areata. Both helper, and cytotoxic T cells promote T-helper1 response with secretion of tumor necrosis factor-α ( TNFα) and interferon-γ ( IFN-γ). T cells have also been found in AA lesions, with increased numbers present in perilesional skin, and so autoimmunity has a role in the etiology of AA. Moreover, genetic susceptibility is a key contributor to disease development. However, disease onset and phenotypic presentation are probably modified by complex environmental interplay and stress. Various cytokines are implicated in the pathogenesis of the disease including macrophage migration inhibitory factor (MIF). Macrophage migration inhibitory factor is a pleiotropic protein exhibiting a broad range of activities. It was first described as a lymphokine that prevents random migration of macrophages, and recruits them at inflammatory loci. Macrophage migration inhibitory factor is located at an upstream position in the events  Summary 88 leading to possible dysregulated immunoinflammatory responses leading to autoimmune reactions, and may therefore represent a new potential target for the treatment of autoimmune diseases. MIF participates in the developmental and effector phases of adaptive cellular and humoral immune response, including antigen-dependent T cell priming and proliferation, delayed type hypersensitivity and antibody production. MIF is involved in the pathogenesis of other autoimmune disease as SLE and vitiligo. MIF stimulates the expression, and secretion of the proinflammatory cytokines, TNFα, IFN-γ, IL-1, IL-6 and IL-8. It was observed that there was an increased level of these cytokines in alopecia areata which may suggest the role of MIF in the pathogenesis of alopecia areata. So, in the present study we aimed to assess the serum and skin level of MIF in the alopecia areata, and we are looking forward to the application of the anti MIF biological therapy that might give us glimpse hope in the treatment of the disease. This work was carried out on 30 patients with alopecia areata with different grades of severity and 15 apparently healthy age and sex matched control subjects. Serum and skin biopsy MIF level was measured by ELISA technique. In the present study, there was a significant elevation in both serum and skin biopsy MIF levels in AA patients in comparison to control subjects, there was also positive relation between MIF levels and severity of AA, disease duration, and psychological stressor present among alopecia patients from the disease. There  Summary 89 was also a negative correlation between MIF level and age of patients, i.e. the young age had a higher level of MIF. In conclusion, MIF seems to have an important role in the aetiopathogenesis of autoimmune skin diseases including alopecia areata. It could thus be a promising target in the therapy of the disease as it is the only cytokine that counteracts the glucocorticoid mediated inhibition of proinflammatory cytokines. This may be the critical factor limiting the immunosuppressive effects of glucocorticoid therapy in treatment of autoimmune diseases. Several pharmaceutical companies have already followed different strategies in the development of MIF blocking reagents in the treatment of immunoinflammatory diseases. Anti-MIF could be added as one of the new biological treatments for alopecia areata. Further understanding of the function and regulation of MIF might be of great value for the introduction of new therapeutic approaches for some dermatologic and non dermatologic diseases