n−3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases

Abstract

Inflammation is part of the normal host response to infection and injury. However, excessive or inappropriate inflammation contributes to a range of acute and chronic human diseases and is characterized by the production of inflammatory cytokines, arachidonic acid-derived eicosanoids (prostaglandins, thromboxanes, leukotrienes, and other oxidized derivatives), other inflammatory agents (eg, reactive oxygen species), and adhesion molecules. At sufficiently high intakes, long-chain nҀ3 polyunsaturated fatty acids (PUFAs), as found in oily fish and fish oils, decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species and the expression of adhesion molecules. Long-chain nҀ3 PUFAs act both directly (eg, by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly (eg, by altering the expression of inflammatory genes through effects on transcription factor activation). Long-chain nҀ3 PUFAs also give rise to a family of antiinflammatory mediators termed resolvins. Thus, nҀ3 PUFAs are potentially potent antiinflammatory agents. As such, they may be of therapeutic use in a variety of acute and chronic inflammatory settings. Evidence of their clinical efficacy is reasonably strong in some settings (eg, in rheumatoid arthritis) but is weak in others (eg, in inflammatory bowel diseases and asthma). More, better designed, and larger trials are required to assess the therapeutic potential of long-chain nҀ3 PUFAs in inflammatory diseases. The precursor nҀ3 PUFA ␣-linolenic acid does not appear to exert antiinflammatory effects at achievable intakes.Am J Clin Nutr 2006;83(suppl):1505S-19S.

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

“…The primary cellular origin of IL‐1β in atherosclerosis is unclear, but we have previously shown in coronary atherosclerotic plaques of patients with IHD that IL‐1β is predominantly expressed in relatively large amounts in the endothelium and vasa vasorum 75. We did show robust reductions in IL‐8, RANTES, and MCP‐1 in plasma, although previous animal studies have reported no significant correlation between DHA feeding and these plasma cytokines 76. Most of these studies, however, were small and used fish oil, with little attention given to specific DHA effects.…”

Long-chain polyunsaturated fatty acids: Selected mechanisms of action on bone

“…In line with this finding, the PUFA composition of cell membranes is dependent on the dietary intake to a great extent. It has been shown, for instance, that when humans ingest fish products, the n-3 PUFAs EPA and DHA from the diet partially replace the n-6 PUFAs, especially AA, in cell membranes [14,15].…”

“…[11,34,117]. PGE 2 , an AA metabolite, has also been shown to stimulate IL-6 production [15]. There is in vitro evidence of cross-talk between the COX-2/PGE 2 and IL-6 systems [118] in murine osteoblast-osteoclast co-cultures that results in increased osteoclastogenesis via effects on the RANK/RANKL/OPG system.…”

Rationale and use of n-3 fatty acids in artificial nutrition

“…There is strong evidence for health benefits of these fatty acids, especially with regard to CVD (33)(34)(35)(36) . They act to modify tissue and blood lipid metabolism, blood lipid concentrations, blood coagulation, immune function, inflammation and endothelial function (37)(38)(39)(40)(41) . EPA and DHA are readily incorporated into cells and tissues and act to modify membrane properties, eicosanoid profiles, signal transduction processes and gene expression (11,12) .…”