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

Guixiang Zhao, Terry D. Etherton, Keith R. Martin, Peter J. Gillies, Sheila Grace West, Penny Margaret Kris-Etherton

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216 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)385-391
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Issue number2
StatePublished - Feb 1 2007


All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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