Anti-inflammatory Effect of Polyunsaturated Fatty Acid N-Acylethanolamines Mediated by Macrophage Activity In Vitro and In Vivo

Abstract

In recent years, there has been increasing interest in studying the anti-inflammatory activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines, NAE), which are highly active lipid mediators. The results of this study demonstrate that a dietary supplement (DS) of fatty acid-derived NAEs reduces LPS-induced inflammation. The processes of cell proliferation, as well as the dynamics of Iba-1-, CD68-, and CD163-positive macrophage activity within the thymus and spleen were studied. The production of pro-inflammatory cytokines (TNF, IL1β, IL6, and INFγ), ROS, NO, and nitrites was evaluated in the blood serum, thymus, and LPS-stimulated RAW264.7 mouse macrophages. In vitro and in vivo experiments have shown that DS (1) prevents LPS-induced changes in the morphological structure of the thymus and spleen; (2) levels out changes in cell proliferation; (3) inhibits the activity of Iba-1 and CD68-positive cells; (4) reduces the production of pro-inflammatory cytokines (TNF, IL1β, IL6, and INFγ), ROS, and CD68; and (5) enhances the activity of CD-163-positive cells. In general, the results of this study demonstrate the complex effect of DS on inflammatory processes in the central and peripheral immune systems.

Keywords: DHEA; EPEA; Inflammation; Lipopolysaccharide (LPS); Macrophages; N-docosahexaenoylethanolamine; N-eicosapentaenoylethanolamine; Spleen; Thymus.