Inflammation in Rheumatoid Arthritis: The Role of SPMs

Osteoarthritis (OA) and rheumatoid arthritis (RA) are both inflammatory disorders that affect the cartilage and the lining of the joints, respectively. While both are inflammatory conditions that affect the joints, their pathology and symptoms differ. The Mayo Clinic points out that osteoarthritis “occurs when the protective cartilage on the ends of [the] bones wears down over time,” often with age. Alternatively, inflammatory arthritis, or rheumatoid arthritis is an autoimmune disorder that causes painful swelling in the lining of the joints.

Inflammation in Rheumatoid Arthritis

Inflammation in RA is very complex and it can also damage other body systems, such as skin, eyes, lungs, bones, and the vascular system. Indeed, studies have shown that RA progression is correlated with interstitial lung disease and coronary artery calcification, to name a few. Each of the related conditions is also attributed to systemic inflammation throughout the body, highly prevalent in RA.

The pathology of RA is not fully known, but may involve TNFα. A principal pro-inflammatory cytokine, TNFα, is vital for immunity to infection. However, excessive production is associated with autoimmune diseases like RA, a recent review explains. Neutralizing TNFα can ameliorate disease and control symptoms in RA patients, but treatment with TNFα inhibitors may also be ineffective and/or exacerbate the disease. The complex signaling pathways of TNFα are to blame for this paradoxical relationship. The review cites early study results indicating, “effector T cells in patients with RA are hyporesponsive due to chronic exposure to TNFα,” though that relationship has not yet been fully elucidated. 

Managing Inflammation with Lifestyle and SPMs

Many symptoms of arthritis may be managed with healthy lifestyle behaviors. For example, getting regular physical activity, maintaining a healthy weight, and eating an anti-inflammatory diet may slow the progression of symptoms. RA cannot be reversed, though. Due to the systemic inflammation present in RA, other pharmacological therapies are frequently recommended, including supplementation of EPA, DHA, and SPMs to the diet.

EPA and DHA are substrates of mediators that promote resolution of inflammation, also known as SPMs. While research on the applications of specialized pro-resolving mediators in rheumatoid arthritis is in progress, a 2016 review offers a preview of the potential role of SPMs to combat rheumatic diseases like RA. Indeed, the review concludes that, “SPMs might have some potential to a novel therapeutic target for arthritis or any other rheumatic diseases.”

In a randomized trial of 36 patients with inflammatory arthritis, participants were randomized to take n-3 polyunsaturated fatty acids (PUFA) for four weeks.  The SPMs in their synovial fluid and plasma were measured before and after the trial. E- and D-series SPMs were present in synovial fluid and plasma of the RA patients. Conversion of the n-3 PUFA was greater in the synovial fluid than in plasma, indicating that the SPMs work at the site of inflammation, in addition to working systemically. Furthermore, some SPMs have elsewhere been found to have a function of reducing tissue damage in patients with RA.

As research on therapies for RA continues, SPMs may be an important therapeutic option for patients who have the disease. Resolving the inflammation throughout the body and in the synovial fluid and joint linings may help reduce the pain associated with the disease and the reduced quality of life.

References

Barden AE, Moghaddami M, Mas E, et al. Specialised Pro-Resolving Mediators of Inflammation in Inflammatory Arthritis. Prostaglandins Leukot Essent Fatty Acids. 2016;107:24-9.

Bystrom J, Clancy F, Taher TE, et al. TNFα in the regulation of Treg and Th17 cells in rheumatoid arthritis and other autoimmune inflammatory diseases. Cytokine. 2016.

Murakami K. Potential of Specialized Pro-resolving Lipid Mediators Against Rheumatic Diseases. Nihon Rinsho Meneki Gakki Kaishi. 2016;39(3):155-63.

Perez-Dorame R, Mejia M, Mateos-Toledo H, Rojas-Serrano J. Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity. Rheumatol Clin. 2015;11(1):12-6.

Whalin B, Meedt T, Jonsson F, et al. Coronary Artery Calcification is Related to Inflammation in Rheumatoid Arthritis: A Long-Term Follow-Up Study. Biomed Res Int. 2016:1261282.

Yates CM, Calder PC, Ed Rainger G. Pharmacology and Therapeutics of Omega-3 Polyunsaturated Fatty Acids in Chronic Inflammatory Disease. Pharmacol Ther. 2014 Marl141(3):272-82.

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