Macrophage inhibitory factor alters the functionality of macrophages and their involvement in disease pathogenesis of active generalized vitiligo patients

In autoimmune dermatitis patients, a macrophage migration inhibitory factor (MIF) is widely used to determine the severity of the diseases with other clinical parameters. Moreover, in vitiligo, MIF has shown significant positive correlation with the VASI (Vitiligo Area Scoring Index) score of both generalized and localized vitiligo patients. MIF function as pro-inflammatory cytokine and inhibited random migration of macrophages from inflammation loci. Hence, activated macrophage infiltrates promote the diseases pathogenesis. Till date, macrophages and involvement of their secreted MIF in disease severity of vitiligo patients remains undetermined. The frequency of both M1 and M2 macrophages was evaluated in active GV patients (n = 20) using flow cytometry in blood and in tissues by confocal microscopy (n = 10). Relative m-RNA expression and cytokine profiling of pro and anti-inflammatory mediators were estimated in PBMCs and in serum of patients. Lastly, concentration of nitric oxide and phagocytic activity from macrophages of active patients were calculated to understand the diseases pathology in detail. Both in circulation as well as in tissues, the infiltration of M1 macrophages was increased in active GV patients, while the percentage of M2 macrophages was comparable to healthy tissues. Aberrant expression of pro and anti-inflammatory molecules including IL-1β, IL-6, TNF-α, IL-12 and MIF impair the cellular hemostasis and induce systematic inflammation. Elevated nitric oxide and higher phagocytic activity of macrophages enhanced the destruction and/or depigmentation of melanocytes causing vitiligo. Elevated macrophages in both tissue and blood enhanced the secretion of MIF and other inflammatory mediators that further enforce the production of nitric oxide, activation and phagocytic activity of macrophages against melanocytes and melanocytes antigens. As a result, destruction of melanocytes and melanin production occurred and caused the depigmentation and/or white macules on the skin.