α-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

Abstract

!-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 Thomas Brzoska,* Thomas A. Luger, Christian Maaser, Christoph Abels, and Markus Bo¨hm* Department of Dermatology (T.B., T.A.L., M.B.), University of Mu¨nster, Mu¨nster, Germany; Wolff Arzneimittel (T.B., C.A.), Bielefeld, Germany; and Department of Internal Medicine (C.M.), University of Mu¨nster, Mu¨nster, Germany !-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over the last few years have provided evidence that !-MSH has potent protective and antiinflammatory ef- fects. These effects can be elicited via centrally expressed melanocortin receptors that orchestrate descending neuro- genic antiinflammatory pathways. !-MSH can also exert an- tiinflammatory 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 an- tiinflammatory effects of !-MSH have been validated in ani- mal models of experimentally induced fever; irritant and al- lergic 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 ef- fect but lack of pigmentary action, the C-terminal tripeptide of !-MSH, KPV, has been delineated as an alternative for an- tiinflammatory ther

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