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 imp ortant effects on monocyte/macrophage cell lines, regulating the secre tion of several cytokines, and the production of eicosanoids. In human monocytes and macrophages, IL-4 increases the expression of 15-lipoxy genase and 15-HETE production, but suppresses the inducible isoform of the prostaglandin H synthase (PGHS-2) enzyme and prostanoid synthesis . Prostanoids, in particular prostaglandin E-2 (PGE(2)) have important functions in modulating inflammatory and fibrotic processes. We compa red the effect of IL-4 on the expression of PGHS-2 in human alveolar m acrophages (AM) and blood monocytes (BM) activated with physiologicall y distinct stimuli, lipopolysaccharide (LPS) or IL-l in vitro. The ind uction of PGHS-2 mRNA and protein, and prostanoid synthesis by all sti muli was inhibited by exogenous IL-4 in both cell types. However, mono cytes were more susceptible to this effect of IL-4 than alveolar macro phages. (C) 1997 by Elsevier Science Inc.