The influence of anti-inflammatory lipoxin A4 on generation of cytokines by peripheral blood mononuclear cells of patients with psoriatic arthritis

Background: Up to 40% of patients with psoriasis suffer from pso-riatic arthritis (PsA), an underrecognized inflammatory arthropathy of incompletely understood pathogenesis. PsA affects axial joints, surrounding ligaments, tendons and entheses. One hypothesis links repeated microinjuries with disorders of inflammation resolution me-chanisms that lead to chronic inflammation, which spreads to surro-unding tissues. An example of the mediators which lead to resolution of inflammation in physiological conditions are derivatives of arachi-donic acid - lipoxins. Objectives: The aim of the study was to compare if the influence of lipoxin A4 on the synthesis of pro-inflammatory cytokines by peri-pheral blood mononuclear cells (PBMCs) isolated from peripheral blo-od of patients with PsA and healthy individuals. Methods: 10 patients with PsA and 5 matching healthy controls were enrolled in the study. PBMSc were isolated by gradient-density cen-trifugation technique and incubated with lipopolysaccharide with or without the addition of lipoxin A4 for 24 hours. The levels of IL-1 beta, IFN-alpha, IFN-gamma, TNF alpha, MCP-1, IL-6, IL-8, IL-10, IL-17, IL-12, IL-18, IL-23 and IL-33 in cell culture supernatants were quantified by cytometric bead array system. Results: Incubation of PBMCs with LPS, increased production of all cytokines assessed either in patients with psoriatic arthritis or in heal-thy controls. In PBMCs from healthy controls incubation of cells with lipoxine A4 decrease production of proinflammatory cytokines. Howe-ver, in patients with psoriatic arthritis addition of lipoxine A4 did not inhibited LPS - induced proinflammatory cytokines release. Conclusions: The anti-inflammatory effect of lipoxin A4 is reversed in PsA PBMCs, supporting the hypothesis of defective resolution of in-flammation in the pathogenesis of PsA.