Activation of inflammation and resolution pathways of lipid mediators in synovial fluid from patients with severe rheumatoid arthritis

Background: The upregulation of the cyclooxygenase and lipoxygenase pathways of arachidonic acid is thought to be involved in the development of rheumatoid arthritis. Recently, the presence of specialized pro-resolving lipid mediators in synovial tissues from patients with osteoarthritis has been reported. Objective: To clarify the quantitative and qualitative changes in lipid mediators in the synovium of severe rheumatoid arthritis patients, we compared the profiles of lipid mediators in synovial fluid obtained from patients with severe rheumatoid arthritis and from those with severe osteoarthritis. Methods: We enrolled 18 patients with rheumatoid arthritis and 26 patients with osteoarthritis. All the patients had undergone total knee replacement surgery. Synovial fluid samples had been obtained during the surgery. Lipid profiling in the synovial fluid from these patients was performed using liquid chromatography-tandem mass spectrometry/mass spectrometry. Results: Among the 150 oxidized fatty acids examined so far, 119 were substantially detected in synovial fluid from the patients. Not only the concentrations of pro-inflammatory lipid mediators such as prostaglandins and leukotrienes, but also those of specialized pro-resolving lipid mediators such as lipoxins, resolvins, and protectin D1 were significantly higher in synovial fluid obtained from rheumatoid arthritis patients than from synovial fluid obtained from osteoarthritis patients. Conclusion: The activation of both inflammation and resolution pathways of lipid mediators might be a fatty acid signature in the synovial fluid of patients with severe rheumatoid arthritis. Inflammatory, anti-inflammatory and pro-resolving mediators in synovial fluid could be good biomarkers for differentiating between severe rheumatoid arthritis and severe osteoarthritis.