MAG-EPA resolves lung inflammation in an allergic model of asthma

Summary Background Asthma is a chronic disease characterized by airways hyperresponsiveness, inflammation and airways remodelling involving reversible bronchial obstruction. Omega‐3 fatty acids and their derivatives are known to reduce inflammation in several tissues including lung. Objectives The effects of eicosapentaenoic acid monoacylglyceride (MAG‐EPA), a newly synthesized EPA derivative, were determined on the resolution of lung inflammation and airway hyperresponsiveness in an in vivo model of allergic asthma. Methods Ovalbumin (OVA)‐sensitized guinea‐pigs were treated or not with MAG‐EPA administered per os. Isometric tension measurements, histological analyses, homogenate preparation for Western blot experiments or total RNA extraction for RT‐PCR were performed to assess the effect of MAG‐EPA treatments. Results Mechanical tension measurements revealed that oral MAG‐EPA treatments reduced methacholine (MCh)‐induced bronchial hyperresponsiveness in OVA‐sensitized guinea‐pigs. Moreover, MAG‐EPA treatments also decreased Ca2+ hypersensitivity of bronchial smooth muscle. Histological analyses and leucocyte counts in bronchoalveolar lavages revealed that oral MAG‐EPA treatments led to less inflammatory cell recruitment in the lung of OVA‐sensitized guinea‐pigs when compared with lungs from control animals. Results also revealed a reduction in mucin production and MUC5AC expression level in OVA‐sensitized animals treated with MAG‐EPA. Following MAG‐EPA treatments, the transcript levels of pro‐inflammatory markers such as IL‐5, eotaxin, IL‐13 and IL‐4 were markedly reduced. Moreover, per os MAG‐EPA administrations reduced COX2 over‐expression in OVA‐sensitized animals. Conclusion and Clinical Relevance We demonstrate that MAG‐EPA reduces airway hyperresponsiveness and lung inflammation in OVA‐sensitized animals, a finding consistent with a decrease in IL‐4, IL‐5, IL‐13, COX‐2 and MUC5AC expression levels in the lung. The present data suggest that MAG‐EPA represents a new potential therapeutic strategy for resolving inflammation in allergic asthma.