The alpha-melanocyte-stimulating hormone acts as a local immune homeostasis factor in experimental allergic asthma

Background Originally, the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) has been described as a mediator of skin pigmentation. However, recent studies have shown that alpha-MSH is able to modulate inflammation in various tissues including the lung. So far, it is still not clear whether alpha-MSH also plays a role in allergic bronchial asthma. Objective This study aimed at investigating the role and regulatory mechanisms of alpha-MSH in asthma pathogenesis. Methods alpha-MSH levels were measured in bronchoalveolar lavage (BAL) fluid of asthmatic and non-asthmatic individuals as well as of healthy mice and mice with experimental asthma. Wild-type mice were sensitized to ovalbumin (OVA) and exposed to an OVA aerosol in order to induce experimental allergic asthma. alpha-MSH was administrated intratracheally, the alpha-MSH antibody intraperitoneally prior each OVA challenge. Airway inflammation, cytokine production, mucus production, airway hyperresponsiveness and receptor expression were assessed. Results alpha-MSH levels in BAL of asthmatic individuals and mice were significantly higher compared to healthy controls. In a mouse model of experimental asthma, alpha-MSH neutralization increased airway inflammation and mucus production, whereas local administration of alpha-MSH significantly reduced inflammation of the airways. The beneficial effects were further associated with decreased levels of eosinophilic chemoattractant factors that are released by MC5R-positive T helper 2 and airway epithelial cells. Conclusion and Clinical Relevance alpha-MSH acts as a regulatory factor to maintain local immune homeostasis in allergic bronchial asthma.