An in vitro examination of the interaction between dietary fatty acids and phenotype‐related behavior of alveolar macrophages

We hypothesize that a diet high in n‐6 and low in n‐3 fatty acids facilitates a bias toward the humoral‐mediated immunity associated with allergic airway disease. A shift related to an imbalance of n‐6/n‐3 fatty acids is postulated to be the result of an increased presence of prostaglandin (PGE 2 ) that subsequently signals changes in T‐helper cell signaling and B‐lymphocyte antibody production. The purpose of this investigation was to examine PGE 2 and pro‐inflammatory cytokine (TNFα, IL‐6) output in response to n‐6/n‐3 fatty acid ratios found in the Western diet. Transformed porcine alveolar macrophages (3D4/31 cells) were cultured under physiological conditions. Growth media was supplemented with 10% lipid‐stripped porcine serum. Cells were exposed to arachidonic acid (AA), ecosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) for 72 hours in single doses (2.5, 25, 50 μM) and in combination (AA/EPA and AA/DHA) at ratios of 2:1, 10:1, and 20:1. A positive linear dose response to AA was observed for PGE 2 , while the opposite occurred with EPA and DHA (p < 0.01). TNFα and IL‐6 concentrations versus controls did not change. However, AA/EPA resulted in both a linear elevation of PGE 2 (p < 0.05) and reduction of TNFα (p < 0.01). These data suggest that alveolar macrophages may undergo a selective change in inflammatory signal phenotype that favors PGE 2 release, humoral‐mediated immunity, and allergic airway disease. Supported by UNH Experimental Station Project H495.