Abstract

[Introduction or background] Ghrelin, an appetite-stimulating peptide, has been reported to have anti-inflammatory effect in the airway. However, ghrelin has an extremely short half-life and a limited route of administration. On the other hand, anamorelin, a ghrelin receptor agonist, has already been approved in Japan as a therapeutic agent for malignant cachexia, and is also orally administrable, with established safety. Therefore, in this study, we investigated the inhibitory effects of anamorelin on allergic airway inflammation in experimental mouse model of asthma. [Methods] Allergic airway inflammation was induced in 5-week-old BALB/c mice by intraperitoneal injection of dust mite antigen followed by five days of intranasal administration. Anamorelin was orally administered for an additional five days in conjunction with dust mite antigen inhalation. Airway hyperresponsiveness (AHR) was analyzed using a flexiVent system and inflammation was evaluated through bronchoalveolar lavage fluid (BALF) and lung tissue analyses. [Results] Anamorelin significantly suppressed the increase of AHR and inhibited the infiltration of eosinophils in the subcutaneous airway epithelium of mouse model of allergic inflammation. Percentage of goblet cell (PAS positive cells) in bronchial epithelium was also reduced by anamorelin treatment. There was a trend toward lower eosinophiles, with a significant decrease in neutrophiles in BALF. No significant difference in body weight change was observed. [Conclusion] Anamorelin is expected to have inhibitory effects on allergic airway inflammation.