Influence of Dietary n-3 Long Chain Polyunsaturated Fatty Acid Intake on Oxylipins in Erythrocytes of Women with Rheumatoid Arthritis.

Oxylipins derived from n-3 fatty acids are suggested as the link between these fatty acids and reduced inflammation. The aim of the present study was to explore the effect of a randomized controlled cross-over intervention on oxylipin patterns in erythrocytes. Twenty-three women with rheumatoid arthritis completed 2 × 11-weeks exchanging one cooked meal per day, 5 days a week, for a meal including 75 g blue mussels (source for n-3 fatty acids) or 75 g meat. Erythrocyte oxylipins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were analyzed with multivariate data analysis. Orthogonal projections to latent structures (OPLS) with effect projections and with discriminant analysis were performed to compare the two diets' effects on oxylipins. Wilcoxon signed rank test was used to test pre and post values for each dietary period as well as post blue-mussel vs. post meat. The blue-mussel diet led to significant changes in a few oxylipins from the precursor fatty acids arachidonic acid and dihomo-É£-linolenic acid. Despite significant changes in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and free EPA in erythrocytes in the mussel group, no concurrent changes in their oxylipins were seen. Further research is needed to study the link between n-3 fatty-acid intake, blood oxylipins, and inflammation.

Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults.

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.

JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease marked by bone and cartilage destruction. Current biologic therapies are beneficial in only a portion of patients; hence small molecules targeting key pathogenic signaling cascades represent alternative therapeutic strategies. Here we show that c-Jun N-terminal kinase (JNK) 1, but not JNK2, is critical for joint swelling and destruction in a serum transfer model of arthritis. The proinflammatory function of JNK1 requires bone marrow-derived cells, particularly mast cells. Without JNK1, mast cells fail to degranulate efficiently and release less IL-1ß after stimulation via Fcγ receptors (FcγRs). Pharmacologic JNK inhibition effectively prevents arthritis onset and abrogates joint swelling in established disease. Hence, JNK1 controls mast cell degranulation and FcγR-triggered IL-1ß production, in addition to regulating cytokine and matrix metalloproteinase biosynthesis, and is an attractive therapeutic target in inflammatory arthritis.