Dietary α-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects

• Published in: The American journal of clinical nutrition Vol. 85; no. 2; pp. 385 - 391
• Main Authors: Zhao, Guixiang, Etherton, Terry D, Martin, Keith R, Gillies, Peter J, West, Sheila G, Kris-Etherton, Penny M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.02.2007; American Society for Clinical Nutrition
• Subjects: Adult; Aged; alpha-Linolenic Acid - metabolism; alpha-Linolenic Acid - pharmacology; anti-inflammatory activity; Biological and medical sciences; blood cells; cardioprotective effect; cytokines; Cytokines - biosynthesis; Cytokines - drug effects; diet-related diseases; dietary fat; Dietary Fats - metabolism; Dietary Fats - pharmacology; experimental diets; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Humans; hypercholesterolemia; Hypercholesterolemia - metabolism; inflammation; inhibitors; interleukins; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; linolenic acid; Male; men; menopause; Middle Aged; Overweight; Postmenopause; Vertebrates: anatomy and physiology, studies on body, several organs or systems; women; Human; peripheral blood mononuclear cells; Hypercholesterolemic subjects; tumor necrosis factor-a; Cytokine; Metabolic diseases; Interleukin 1β; Lipids; Hyperlipoproteinemia; Inflammation; Lipoprotein; Cholesterol; Interleukin 6; Blood cell; Hypercholesterolemia; Linolenic acid; Mononuclear cell; Tumor necrosis factor; α-linolenic acid; Dyslipemia; Eicosapentaenoic acid; eicosapentaenoic acid,interleukin-6,interleukin-1β
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/85.2.385

BACKGROUND:Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in α-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects. OBJECTIVE:The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMCs) from subjects fed the experimental diets. DESIGN:A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (n = 23) were assigned to 3 experimental diets: a diet high in ALA (ALA diet; 6.5% of energy), a diet high in linoleic acid (LA diet; 12.6% of energy), and an average American diet (AAD) for 6 wk. Serum interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) concentrations and the production of IL-6, IL-1β, and TNF-α by PBMCs were measured. RESULTS:IL-6, IL-1β, and TNF-α production by PBMCs and serum TNF-α concentrations were lower (P < 0.05 and P < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-α was inversely correlated with ALA (r = -0.402, P = 0.07) and with eicosapentaenoic acid (r = -0.476, P = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-α produced by PBMCs (r = -0.423, P < 0.05). CONCLUSIONS:Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1β, and TNF-α production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-α release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.