Differential sensitivities of human blood monocytes and alveolar macrophages to the inhibition of prostaglandin endoperoxide synthase-2 by interleukin-4

Interleukin-4 (IL-4) is a potent immunomodulatory cytokine synthesized and released by Th2 lymphocytes, mast cells and basophils. It has important effects on monocyte/macrophage cell lines, regulating the secretion of several cytokines, and the production of eicosanoids. In human monocytes and macrophages, IL-4 increases the expression of 15-lipoxygenase and 15-HETE production, but suppresses the inducible isoform of the prostaglandin H synthase (PGHS-2) enzyme and prostanoid synthesis. Prostanoids, in particular prostaglandin E2 (PGE2) have important functions in modulating inflammatory and fibrotic processes. We compared the effect of IL-4 on the expression of PGHS-2 in human alveolar macrophages (AM) and blood monocytes (BM) activated with physiologically distinct stimuli, lipopolysaccharide (LPS) or IL-1 in vitro. The induction of PGHS-2 mRNA and protein, and prostanoid synthesis by all stimuli was inhibited by exogenous IL-4 in both cell types. However, monocytes were more susceptible to this effect of IL-4 than alveolar macrophages.