Prostaglandin e₂ and tumour necrosis factor-α release by monocytes are modulated by phospholipids

The regulation of pro- and anti-mediator release from cells within the alveolar space would represent a desirable mechanism serving to protect this delicate gas-exchanging region of the lung. This study investigates the effect of alveolar surfactant lipids on the regulation of tumour necrosis factor alpha (TNF-α), a potent inflammatory cytokine, and prostaglandin E₂ (PGE₂), a lipid mediator with anti-inflammatory properties. The results of this investigation reveal a marked effect on the release of these two important mediators from a monocytic cell line, MonoMac 6 (MM6), by phosphatidylcholine (PC), phosphatidylethanolamine (PE), cholesterol (Chol) and sphingomyelin (SM). PC, PE and Chol demonstrated marked downregulation of TNF-α production at lipid concentrations of 125 and 250 μg/ml. Interestingly, SM significantly up regulated the release of TNF-α at these concentrations. However, the release of PGE₂ in MM6 cells incubated with the same lipids was significantly increased with PC and Chol, and significantly decreased in cells pre-treated with SM. This indicates a role for these lipids in alveolar immunoregulation. (C) 2000 Academic Press.