Oleoylethanolamide induces eosinophilic airway inflammation in bronchial asthma.

Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils. Oleoylethanolamide (OEA), an endocannabinoid similar to those found in cannabis, occurs naturally in the body, and has now been implicated in promoting symptoms of asthma. OEA activates white blood cells called eosinophils and ILC2 cells, which are both parts of our immune response. Researchers in South Korea, led by Ga-Young Ban at Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, studied the effect of OEA on respiratory system cells from people with asthma and in mice used to model the condition in humans. OEA-induced inflammatory responses associated with asthma by stimulating the release of signaling molecules called cytokines. However, some other endocannabinoids have anti-inflammatory effects. Studying the effects of all endocannabinoids could yield new insights into asthma, with this study opening new possibilities for treating asthma by interfering with OEA-induced signaling responses.