α-melanocyte acts as an anti-inflammatory regulator in allergic bronchial asthma

The complex phenotype of allergic bronchial asthma arises from a chronic inflammatory response in the airways, which is regulated on different levels. On the one hand the balance between T helper (TH) 1 and TH2 type immune responses, which is essential for the initiation of allergic inflammation, and on the other hand the balance between pro- and anti-inflammatory mediators regulating the maintenance of the inflammatory response. One of these anti-inflammatory mediators could be the α-melanocyte-stimulating hormone (α-MSH), which has originally been described to stimulate melanin production in the skin. This study aimed at investigating the role of α-MSH in asthma pathogenesis.

In mouse models of acute and chronic experimental allergic asthma we found that α-MSH is produced in inflamed airways and that the amount of α-MSH released into the broncho-alveolar lumen increases with intensity and duration of allergic airway inflammation. Using immuno-histology we identified the airway epithelium as the main producer of α-MSH. From the five melanocortin receptors (MC-R) that have been identified so far, we found expression of only MC5-R in healthy animals, mainly by airway epithelial cells. In contrast, asthmatic animals displayed expression of MC5-R not only in the airway epithelium, but also in infiltrating eosinophils. Additionally, we detected expression of MC1-R, which is not expressed in healthy animals, by infiltrating neutrophils and fibroblasts in the tunica adventitia of inflamed vessels. Furthermore, in asthmatic mice neutralization of α-MSH by application of a specific antibody resulted in augmented infiltration of eosinophils into the airways, while intra-tracheal application of α-MSH significantly reduced airway inflammation as well as airway hyperresponsiveness (AHR).

These data indicate that α-MSH acts as an anti-inflammatory regulator of the inflammatory response underlying formation of allergic bronchial asthma.