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.
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