title: Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in alpha-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.
  
  
  METHODS
  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-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations and the production of IL-6, IL-1beta, and TNF-alpha by PBMCs were measured.
  
  
  RESULTS
  IL-6, IL-1beta, and TNF-alpha production by PBMCs and serum TNF-alpha 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-alpha 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-alpha produced by PBMCs (r = -0.423, P < 0.05).
  
  
  CONCLUSIONS
  Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1beta, and TNF-alpha production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-alpha release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhao
authors.forename: Terry D
authors.initials: TD
authors.lastname: Etherton
authors.forename: Keith R
authors.initials: KR
authors.lastname: Martin
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gillies
authors.forename: Sheila G
authors.initials: SG
authors.lastname: West
authors.forename: Penny M
authors.initials: PM
authors.lastname: Kris-Etherton
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects*; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050177:Overweight; D017698:Postmenopause; D017962:alpha-Linolenic Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D017962:alpha-Linolenic Acid