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Modulation of Lipopolysaccharide‐Induced Inflammatory Cytokine Storm by Ultramicronized N‐Palmitoylethanolamine

The anti‐inflammatory effect of the N‐palmitoylethanolamine (PEA) has been widely investigated. PEA is able to inhibit mast cells degranulation and stabilize mitochondrial function. Its mechanism of action involves the cytokine storm management induced by the inflammatory stimuli. The heterogeneous particle size and lipid nature of naïve PEA limit its solubility and become a therapeutic issue. The ultramicronized form of PEA (PEA‐um) has shown better bioavailability than the naïve form. This study investigated the effect of PEA‐um on LPS‐induced lung inflammatory response. Mice were intratracheally instilled with Lipopolysaccharide (LPS), and then PEA‐um (30 mg/kg) was administered at one and six hours later. PEA‐um significantly suppressed the levels of interleukin‐ 6, interleukin‐1 beta and tumor necrosis factor‐alpha, as well as the number of inflammatory cells in bronchoalveolar lavage fluid. Additionally, it decreased lung injury, lactate dehydrogenase and myeloperoxidase activities, wet weight/dry weight ratio and improved superoxide dismutase activity. PEA‐um administration reduced mast cells recruitment in the inflamed tissue. It was also able to decreased the inducible nitric oxide synthase, nitrotyrosine and PARP expressions. Besides, PEA‐um significantly suppressed nuclear factor‐kappa B (NF‐κB) activation in lung tissue. Together, these results indicated that the anti‐inflammatory effect of PEA‐um is associated with the NF‐κB pathway, and that it shows therapeutic potential for LPS‐induced acute lung injury.