Low levels of pro-resolving lipid mediators lipoxin-A4, resolvin-D1 and resolvin-E1 in patients with rheumatoid arthritis

Graphical figure: Lipid mediators and enzymes involved in inflammation and resolution. Arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid are the main precursors of lipid metabolites involved in inflammation. 5-lipoxygenase (5-LOX) is the most critical enzyme in the production of 15-Hydroxyeicosatetraenoic acid (15-HPETE) which that the precursor of the leukotrienes (LTs) responsible for the formation and maintenance of proinflammatory response. LTs are very potent chemotactic molecules and increase proinflammatory cytokine production from immune cells and the production of reactive oxygen species and phagocytosis. For the resolution of inflammation, lipoxins (LXs) and resolvins (Rvs) are synthesized from the same lipid precursors by enzymes cyclooxygenase-2 (Cox-2), P450, 5-LOX, 12-LOX, and 15-LOX. However, these metabolites antagonize the proinflammatory effect of LTs. [Display omitted] •Rheumatoid arthritis is a chronic disease in which pro-inflammatory and anti-inflammatory balance is impaired.•Lipoxin A4, Resolvin D1 and Resolvin E1 are lipid metabolites with strong immunomodulatory effects.•Patients with rheumatoid arthritis have lower Lipoxin A4, Resolvin D1 and Resolvin E1 levels compared to healthy individuals.•These low levels are independent of disease activities of patients with rheumatoid arthritis. Rheumatoid arthritis (RA) is a disease in which joint inflammation is at the forefront but the whole body is affected, and prevention of inflammation is the main treatment approach. Lipoxins (LXs) and resolvins (Rvs) are critical molecules in the resolution of inflammation. In this study, we aimed to investigate the role of LXs and Rvs in the RA pathogenesis. To this end, we measured the LXA 4, RvD 1, RvE 1 levels, and inflammatory cytokines and chemokines IL-6, IL-8, IL-10, IL-17a, IL-22 and MCP-1 in patients with RA and healthy individuals. We found that the LXA4, RvD1, RvE1 levels of the active RA cases were significantly lower than in remission RA and healthy individuals, but the levels of inflammatory cytokines and chemokines were significantly higher. The decreases in LXs and Rvs were independent of disease activity, suggesting that there might be an impairment of LX and Rvs synthesis or catabolism in patients with RA.