A systematic review on the role of eicosanoid pathways in rheumatoid arthritis

Abstract

Background: Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen reduction accompanied by the cartilage degradation. Eicosanoids are responsible for the progressive destruction of cartilage and bone, however neither steroids, nor the non steroidal anti-inflammatory drugs (NSAIDs), cannot slow down cartilage and bone destruction providing only symptomatic improvement. The current rheumatoid arthritis treatment options include mainly the use of disease-modifying anti-rheumatic drugs, the corticosteroids, the NSAIDs and biological agents.

Methods: PubMed, Cochrane, and Embase electronic database were used as the main sources for extracting several articles, reviews, original papers in English for further review and analysis on the implication of arachidonic acid metabolites with rheumatoid arthritis and different strategies of targeting arachidonic acid metabolites, different enzymes or receptors for improving the treatment of rheumatoid arthritis patients.

Results: We first focused on the role of individual prostaglandins and leukotrienes, in the inflammatory process of arthritis, concluding with an outline of the current clinical situation of rheumatoid arthritis and novel treatment strategies targeting the arachidonic acid pathway.

Conclusions: Extended research is necessary for the development of these novel compounds targeting the eicosanoid pathway, by increasing the levels of anti-inflammatory eicosanoids (PGD₂,15dPGJ₂), by inhibiting the production of pro-inflammatory eicosanoids (PGE₂, LTB₄, PGI₂) involved in rheumatoid arthritis or also by developing dual compounds displaying both the COX-2 inhibitor/TP antagonist activity within a single compound.

Keywords: Arachidonic acid pathway; Inflammation; Leukotrienes; Prostaglandins; Rheumatoid arthritis.