Antiinflammatory mediator lipoxin A4 and its receptor in synovitis of patients with rheumatoid arthritis

Abstract

Objective: To evaluate the role of an antiinflammatory lipid mediator, lipoxin A4 (LXA4), in inflammatory arthritis, we measured the level of LXA4 in synovial fluid and lipoxin A4 receptor (ALX) expression in synovial tissues obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods: Levels of LXA4 and its analog (15-epi-LXA4) in synovial fluid from 30 patients with RA and 15 patients with OA were measured by a specific ELISA. Reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and in situ hybridization were performed to detect mRNA for ALX and 15-LOX, and LXA4 synthetase, in synovial tissues from 20 patients with RA and 10 patients with OA. RESULTS Both LXA4 and 15-epi-LXA4 showed significantly higher levels in RA synovial fluid (10.34 +/- 14.12 ng/ml for LXA4) than OA synovial fluid (0.66 +/- 0.77 ng/ml for LXA4). Logarithmic concentration of LXA4 was significantly correlated with that of leukotriene B4 and prostaglandin E2 in RA and OA synovial fluids. Expressions of ALX and 15-LOX mRNA were stronger in RA synovium than OA synovium. Expression of mRNA for interleukin 13 (IL-13), which induces 15-LOX, was significantly stronger in RA synovium than OA synovium.

Conclusion: ALX is an important target of LXA4 in synovial tissues of patients with RA. 15-LOX induced by IL-13 might regulate the production of LXA4 to have an antiinflammatory effect against proinflammatory lipid mediators in inflamed joints. These findings could lead to the development of new therapy for inflammatory arthritis such as RA.