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-Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry, Antiinflammatory and Protective Effects in Vitro and in Vivo, and Future Perspectives for the Treatment of Immune-Mediated Inflammatory Diseases

Department of Dermatology (T.B., T.A.L., M.B.), University of Münster, Münster, Germany; Wolff Arzneimittel (T.B., C.A.), Bielefeld, Germany; and Department of Internal Medicine (C.M.), University of Münster, Münster, Germany

Correspondence: Address all correspondence and requests for reprints to: Markus Böhm, M.D., Associate Professor Department of Dermatology, University of Münster, Von Esmarch-Strasse 58, D-48149 Münster, Germany. E-mail: bohmm{at}uni-muenster.de

-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over the last few years have provided evidence that -MSH has potent protective and antiinflammatory effects. These effects can be elicited via centrally expressed melanocortin receptors that orchestrate descending neurogenic antiinflammatory pathways. -MSH can also exert antiinflammatory and protective effects on cells of the immune system and on peripheral nonimmune cell types expressing melanocortin receptors. At the molecular level, -MSH affects various pathways implicated in regulation of inflammation and protection, i.e., nuclear factor-B activation, expression of adhesion molecules and chemokine receptors, production of proinflammatory cytokines and mediators, IL-10 synthesis, T cell proliferation and activity, inflammatory cell migration, expression of antioxidative enzymes, and apoptosis. The antiinflammatory effects of -MSH have been validated in animal models of experimentally induced fever; irritant and allergic contact dermatitis, vasculitis, and fibrosis; ocular, gastrointestinal, brain, and allergic airway inflammation; and arthritis, but also in models of organ injury. One obstacle limiting the use of -MSH in inflammatory disorders is its pigmentary effect. Due to its preserved antiinflammatory effect but lack of pigmentary action, the C-terminal tripeptide of -MSH, KPV, has been delineated as an alternative for antiinflammatory therapy. KdPT, a derivative of KPV corresponding to amino acids 193–195 of IL-1β, is also emerging as a tripeptide with antiinflammatory effects. The physiochemical properties and expected low costs of production render both agents suitable for the future treatment of immune-mediated inflammatory skin and bowel disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation, and arthritis.