8-11-14-eicosatrienoic-acid and Arthritis--Rheumatoid

Marine n-3 fatty acids and γ-linolenic acid both have anti-inflammatory effects and may be useful to help treat inflammatory diseases. The effects of these alone or combined were examined in patients with arthritis in a randomized controlled trial.. Patients with rheumatoid arthritis or psoriatic arthritis were randomized into four groups in a double-blind, placebo-controlled parallel designed study. Patients received the respective capsules (1: 3.0 g n-3 LC-PUFA/d; 2: 3.2 g γ-linolenic acid/d; 3: 1.6 g n-3 LC-PUFA + 1.8 g γ-linolenic acid/d; 4: 3.0 g olive oil) for a twelve week period. Clinical status was evaluated and blood samples were taken at the beginning and at the end of the period. Differences before and after intervention were tested with paired t-test or with Wilcoxon test for non-normal data distribution.. 60 patients (54 rheumatoid arthritis, 6 psoriatic arthritis) were randomised, 47 finished per protocol. In group 1, the ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA) decreased from 6.5 ± 3.7 to 2.7 ± 2.1 in plasma lipids and from 25.1 ± 10.1 to 7.2 ± 4.7 in erythrocyte membranes (p ≤ 0.001). There was no significant influence on AA/EPA ratio due to interventions in group 2-4. In group 2, the intake of γ-linolenic acid resulted in a strong rise of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte membranes. The combination of n-3 LC-PUFA and γ-linolenic acid (group 3) led to an increase of γ-linolenic acid and dihomo-γ-linolenic acid concentrations in plasma lipids, cholesteryl esters, and erythrocyte mem-branes. This increase was only half of that in group 2.. Incorporation of eicosanoid precursor FAs was influenced by an intake of n-3 LC-PUFA and γ-linolenic acid suggesting a possible benefit for therapy of chronic inflammatory diseases.. ClinicalTrials NCT01179971.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Aged; Aged, 80 and over; Arachidonic Acid; Arthritis, Psoriatic; Arthritis, Rheumatoid; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids, Omega-3; Female; gamma-Linolenic Acid; Humans; Lipid Metabolism; Male; Membrane Lipids; Middle Aged

Topics: 8,11,14-Eicosatrienoic Acid; Arthritis, Rheumatoid; Blotting, Northern; Collagenases; Fibroblasts; Humans; Interleukin-1; Matrix Metalloproteinase 3; Metalloendopeptidases; RNA, Messenger; Synovial Membrane

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.

Topics: 8,11,14-Eicosatrienoic Acid; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acids; Arthritis, Rheumatoid; Dietary Fats, Unsaturated; Fatty Acids, Unsaturated; Fish Oils; gamma-Linolenic Acid; Humans; Linolenic Acids; Phospholipids

Prostaglandins (PG) and related eicosanoids which derive from essential fatty acids are important mediators and modulators of inflammation. Macrophages (M phi), which derive from peripheral blood monocytes (PBM), are prominent cells in the synovium of patients with rheumatoid arthritis (RA), and are a major source of synovial PGE2. In addition, fresh and cultured PBM from RA patients produce more PG than normal control cells. When allowed to mature in culture PBM exhibit many characteristics of macrophages (M-M phi). We examined uptake by M-M phi of eicosanoid precursor fatty acids (FA), their incorporation into cellular phospholipid (PL), and mobilization of FA after cell stimulation. Cultured M-M phi from treated and untreated RA patients (RA M-M phi) took up significantly more linoleic acid (LA), dihomogammalinolenic acid (DHLA) and arachidonic acid (AA) than M-M phi from normal volunteers (N M-M phi). The enhanced uptake of FA observed in 12-day cultures of RA M-M phi was similar to uptake seen in normal human peritoneal macrophages (PM phi). After uptake FA were incorporated mainly into phosphatidylcholine (PC). M-M phi from untreated RA patients incorporated a smaller proportion of [14C]LA into PC (37.0 +/- 12.7% of total PL label) than normal cells (86.0 +/- 4.2%), and a greater proportion of [3H]AA into PC (57.1 +/- 7.1%) than normals (23.9 +/- 6.9%). Stimulation of M-M phi with calcium ionophore A23187 resulted in significantly greater hydrolysis of LA and AA from PC in RA M-M phi from both treated and untreated patients than from PC in N M-M phi. The data indicate that M-M phi from RA patients mature more rapidly in vitro than M-M phi from controls as uptake of FA by RA M-M phi increases with duration of culture and by 12 days in culture equals uptake by normal human peritoneal M phi. Also, RA M-M phi exhibit differences from N M-M phi in uptake, PL distribution, and hydrolysis of eicosanoid precursor FA. Such changes in FA metabolism might influence cell function and inflammatory responses.

Topics: 8,11,14-Eicosatrienoic Acid; alpha-Linolenic Acid; Arachidonic Acid; Arachidonic Acids; Arthritis, Rheumatoid; Calcimycin; Cell Differentiation; Cells, Cultured; Fatty Acids; Humans; Kinetics; Linoleic Acid; Linoleic Acids; Linolenic Acids; Macrophages; Membrane Lipids; Monocytes; Palmitic Acid; Palmitic Acids; Phospholipids; Prostaglandins