title: Impact of the omega-3 to omega-6 polyunsaturated fatty acid ratio on cytokine release in human alveolar cells.
abstract: BACKGROUND
  ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)-induced cytokine release by human alveolar cells was affected by changes in the ω-3/ω-6 ratio of cell membranes induced by different supplies of PUFAs.
  
  
  METHODS
  After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured.
  
  
  RESULTS
  The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin-6, and interleukin-8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti-inflammatory interleukin-10 (P < .001). The balance between proinflammatory and anti-inflammatory cytokines showed an anti-inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001).
  
  
  CONCLUSIONS
  This study showed that proinflammatory cytokine release was dependent on the proportion of ω-3 in the ω-3/ω-6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω-6 to ω-3 in nutrition support of patients with acute lung injury.
authors.affiliation: Department of Anesthesiology and Intensive Care, S. Giovanni Battista Hospital, University of Turin, Turin, Italy. paolo.cotogni@unito.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Cotogni
authors.forename: Giuliana
authors.initials: G
authors.lastname: Muzio
authors.forename: Antonella
authors.initials: A
authors.lastname: Trombetta
authors.forename: V Marco
authors.initials: VM
authors.lastname: Ranieri
authors.forename: Rosa Angela
authors.initials: RA
authors.lastname: Canuto
mesh_terms: D000704:Analysis of Variance; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008962:Models, Theoretical; D011650:Pulmonary Alveoli / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004281:Docosahexaenoic Acids