Pro- and anti-inflammatory bioactive lipids imbalance contributes to the pathobiology of autoimmune diseases

Abstract

Autoimmune diseases are driven by T_H17 cells that secrete pro-inflammatory cytokines, especially IL-17. Under normal physiological conditions, autoreactive T cells are suppressed by TGF-β and IL-10 secreted by microglia and dendritic cells. When this balance is upset due to injury, infection and other causes, leukocyte recruitment and macrophage activation occurs resulting in secretion of pro-inflammatory IL-6, TNF-α, IL-17 and PGE2, LTs (leukotrienes) accompanied by a deficiency of anti-inflammatory LXA4, resolvins, protecting, and maresins. PGE2 facilitates T_H1 cell differentiation and promotes immune-mediated inflammation through T_H17 expansion. There is evidence to suggest that autoimmune diseases can be suppressed by anti-inflammatory bioactive lipids LXA4, resolvins, protecting, and maresins. These results imply that systemic and/or local application of LXA4, resolvins, protecting, and maresins and administration of their precursors AA/EPA/DHA could form a potential therapeutic approach in the prevention and treatment of autoimmune diseases.