Polyunsaturated Fatty Acids and Inflammation: Therapeutic Potential in Rheumatoid Arthritis

The fatty acids of most relevance to inflammatory processes are the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid, the precursor of inflammatory eicosanoids like prostaglandin E2 and leukotriene B4, and the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in rheumatoid arthritis (RA), and the efficacy of nonsteroidal antiinflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. N- 3 PUFAs exert effects on other aspects of immunity relevant to RA like leukocyte chemotaxis, antigen presentation, T cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits of fish oil in patients with RA including reducing pain, duration of morning stiffness and use of non-steroidal antiinflammatory drugs.