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ORIGINAL RESEARCH COMMUNICATION |
-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects1,2,3
1 From the Departments of Nutritional Sciences (GZ, TDE, KRM, and PMK-E), Dairy and Animal Science (TDE), and Biobehavioral Health (SGW), The Pennsylvania State University, University Park, PA, and the DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE (PJG)
Background:Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in 
-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-1ß, and tumor necrosis factor- (TNF-) concentrations and the production of IL-6, IL-1ß, and TNF- by PBMCs were measured.
Results:IL-6, IL-1ß, and TNF- production by PBMCs and serum TNF- 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- 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- produced by PBMCs (r = –0.423, P < 0.05).
Conclusions:Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1ß, and TNF- production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF- release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.
Key Words: Hypercholesterolemic subjects • -linolenic acid • eicosapentaenoic acid • interleukin-6 • interleukin-1ß • tumor necrosis factor- • peripheral blood mononuclear cells
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