2015 ACR/ARHP Annual Meeting: Immune Mediators Can Impact Inflammatory Response

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SAN FRANCISCO—Inflammation can be either acute or chronic, and it’s the inflammatory responses that don’t shut down normally, or resolve, that cause tissue damage in rheumatic disease.
“Resolution bridges the gap between acute inflammation and adaptive immunity,” said Derek W. Gilroy, PhD, head of the Centre for Clinical Pharmacology and Professor of Immunology at University College, London.
Which way the inflammatory process turns at key intervals can depend on certain immune mediators, said a panel of speakers at the at the 2015 ACR/ARHP Annual Meeting on Nov. 7. These mediating factors include fatty acids, such as fish oil in the diet, phagocytes like macrophages that may help clean house after infection or trauma, and various inflammasomes that can trigger a chronic response. Although acute inflammation should go through a quick process to resolution, that’s not always the end of the story. How these mediators behave may tell us more about why some patients’ inflammation turns chronic.

Fish Stories

Omega-3 fatty acids in such foods as fish have been a focus of interest for years as a possible way to influence inflammation through diet or supplementation, said Leslie G. Cleland, MD, FRACP, director of rheumatology at Royal Adelaide Hospital in Australia.

“What messages do we convey to people about dietary, unsaturated fatty acids?” said Dr. Cleland. Omega-3s, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), balance the omega-6 fatty acids found in seed oils used in many processed foods. The omega-6 fatty acids are remodeled to form eicosanoids, which amplify inflammatory responses. EPA and DHA compete for enzymes involved in eicosanoid formation, and tend to reduce the intensity of inflammation. Due to these effects, could adding fish to the diet or taking fish oil supplements play a part in treat-to-target management of rheumatoid arthritis?

Dr. Cleland

“Taking fish oil, while reducing omega-6 fats, is the least expensive and most reliable way to increase n-3, long-chain, polyunsaturated fatty acids in tissues,” he said. Omega-6 fats lead to the production of arachidonic acid, which then triggers prostaglandin production. But dietary omega-3 fats like EPA and DHA are competitive inhibitors of omega-6, and help suppress inflammatory cytokines like IL-1 and TNFα in joint synovial tissue, Dr. Cleland said.

In a long-term study of fish oil as a complementary therapy published in the Annals of the Rheumatic Diseases in 2013, Dr. Cleland and his colleagues looked at how adding a daily supplement of DHA and EPA, along with triple disease-modifying anti-rheumatic drug (DMARD) therapy of methotrexate, sulfasalazine, and hydroxychloroquine, helped improve disease activity scores in patients with early RA.¹ Patients who received 5.5 g of fish oil, compared with controls who received only 0.4 g of fish oil, had lower rates of triple DMARD failure therapy and higher rates of ACR remission. The patients in both groups reported similar rates of DAS28 scores and adverse events, Dr. Cleland noted.