docosapentaenoic-acid and Arthritis--Rheumatoid

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cohort Studies; Docosahexaenoic Acids; Fatty Acids, Unsaturated; Humans; Lipoxins; Synovial Fluid; Treatment Outcome

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines and eicosanoids involved in RA pathogenesis. The aim of this study was to determine the therapeutic potential of ω3 monoglyceride (MAG-ω3) compounds in an in vivo rat model of RA induced by Complete Freund's Adjuvant (CFA).. CFA rats were untreated or treated per os with three specific compounds, namely, MAG-docosahexaenoic acid (MAG-DHA), MAG-eicosapentaenoic acid (MAG-EPA) and MAG-docosapentaenoic acid (MAG-DPA). Morphological and histological analyses, as well as pro-inflammatory marker levels were determined following MAG-ω3 treatments.. Morphological and histological analyses revealed that MAG-EPA and MAG-DPA exhibited strong activity in reducing the progression and severity of arthritic disease in CFA rats. Following MAG-EPA and MAG-DPA treatments, plasma levels of the pro-inflammatory cytokines; interleukin 17A (IL-17A), IL-1β, IL-6 and tumor necrosis factor α (TNFα) were markedly lower when compared to CFA-untreated rats. Results also revealed a decreased activation of p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappa B (NFκB) pathways correlated with a reduced expression of TNFα, cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2) and MMP-9 in paw homogenates derived from MAG-EPA and MAG-DPA-treated rats. Of interest, the combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in CFA rats.. Altogether, the present data suggest that MAG-EPA, without vitamin E, represents a new potential therapeutic strategy for resolving inflammation in arthritis.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Blotting, Western; Cyclooxygenase 2; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Unsaturated; Female; Inflammation; Interleukin-17; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Monoglycerides; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats, Inbred Lew; Severity of Illness Index; Tumor Necrosis Factor-alpha