The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS Patients

Abstract

Background. This study investigated whether the 1 : 2 ω-3/ω-6 ratio may reduce proinflammatory response in human alveolar cells (A549) exposed to anex vivoinflammatory stimulus (bronchoalveolar lavage fluid (BALF) of acute respiratory distress syndrome (ARDS) patients).Methods. We exposed A549 cells to the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA) were added as docosahexaenoic acid (DHA,ω-3) and arachidonic acid (AA,ω-6) in two ratios (1 : 2 or 1 : 7). 24 hours later, in culture supernatants were evaluated cytokines (TNF-α, IL-6, IL-8, and IL-10) and prostaglandins (PGE2and PGE3) release. The FA percentage content in A549 membrane phospholipids, content of COX-2, level of PPARγ, and NF-κB binding activity were determined.Results. The 1 : 2 DHA/AA ratio reversed the baseline predominance ofω-6 overω-3 in the cell membranes (P< 0.001). The proinflammatory cytokine release was reduced by the 1 : 2 ratio (P< 0.01 to <0.001) but was increased by the 1 : 7 ratio (P< 0.01). The 1 : 2 ratio reduced COX-2 and PGE2(P< 0.001) as well as NF-κB translocation into the nucleus (P< 0.01), while it increased activation of PPARγand IL-10 release (P< 0.001).Conclusion. This study demonstrated that shifting the FA supply fromω-6 toω-3 decreased proinflammatory mediator release in human alveolar cells exposed to BALF of ARDS patients.