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Background: ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have opposing influences upon inflammation. Our objective was to determine whether lipopolysaccharide (LPS)-induced cytokine release by human alveolar cells was affected by changes of the ω-3/ω-6 ratio in cell membranes induced by different PUFA supplies. Methods: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω-3) plus arachidonic acid (AA, ω-6) in four different DHA/AA ratios (1: 1, 1: 2, 1: 4, and 1: 7) and cytokine release was 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 pro-inflammatory cytokines (TNF-α, IL-6, and IL-8) was reduced by 1: 1 and 1: 2 DHA/AA ratios (p<. 01 to<. 001), but increased by 1: 4 and 1: 7 DHA/AA ratios (p<. 01 to<. 001) vs. control. The 1: 1 and 1: 2 ratios increased the release of anti-inflammatory IL-10 (p<. 001). The balance between pro-and antiinflammatory 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 pro-inflammatory cytokine release was dependent on the proportion of ω-3 in ω-3/ω-6 ratio in alveolar cell membranes, being reduced with the supply of high proportion of DHA and increased with high proportion of AA, respectively. Our results support the biochemical basis for current recommendations to shift the PUFA supply from ω-6 to ω-3 in nutrition of acute lung injury patients.