Resolvin D1 protects from neutrophil mediated joint destruction in inflammatory arthritis (146.5)

Abstract

Dietary supplementation with omega‐3 PUFA is efficacious in reducing joint pain, morning stiffness and NSAID usage in rheumatoid arthritis patients. Yet there is an unmet need to determine how they exert beneficial effects. Recent discoveries have determined that omega‐3 PUFA can be enzymatically converted in vivo to novel pro‐resolving bioactive lipid mediators, termed resolvins. We recently showed that resolvin D1 (RvD1) limits PMN recruitment in experimental peritonitis via its receptor ALX (PMID:22499990), yet whether RvD1 exhibits anti‐arthritic effects remains to be determined. In an inflammatory arthritis model; mice were administered veh (0.1% EtOH, i.p.) or treated with 17R‐RvD1 (100ng, i.p. daily) either prophylactically (day 0) or therapeutically (ensuing overt signs of arthritis; day 4), and graded for arthritis severity (max score 12). Prophylactic treatment with RvD1 significantly lowered the clinical score and hind paw oedema, and attenuated leukocyte infiltrate and prostanoids within the paw. Importantly, therapeutic treatment reduced the peak in arthritis severity and shortened the resolution interval. Protective actions of RvD1 were abolished in ALX (fpr2/3) null mice, indicating the crucial role of this GPCR in RvD1 joint protective actions. These studies indicate that the pro‐resolving mediator RvD1 offers a valuable therapeutic approach for inflammatory joint diseases including rheumatoid arthritis.Grant Funding Source: Supported by Arthritis Research UK Fellowship 19909 to LVN and The Wellcome Trust 086867/Z/08/Z