Retinoic acid inhibits interleukin‐1‐induced cytokine synthesis in human monocytes

Retinoids are pluripotent morphogens whose effects on gene expression are mediated through specific intracellular receptors. They have certain anti-infiamma- tory effects in vivo, the basis of which is not clearly un- derstood. To characterize mechanisms involved with potential anti-inflammatory actions of retinoids, we studied the effects of retinoic acid (RA) on cytokine production in human peripheral blood monocytes. RA differentially modulated the expression of interleukin-1f3 (IL-1f3), IL-6, and IL-8 mRNAs depending on the induc- ing stimulus. While phorbol myristate acetate-induced IL-113 and IL-8 mRNA expression was increased by RA (IL-6 could not be induced by this pathway in mono- cytes), IL-1f3-induced expression of IL-113 and IL-8 was markedly reduced and IL-6 gene expression was almost completely suppressed. Lipopolysaccharide (LPS)-induced cytokine synthesis was only slightly reduced and this re- quired a longer preincubation ( > 72 h) of monocytes with RA. IL-i-induced de novo synthesis of IL-6 protein and secretion of biologically active IL-fl were also inhibited by RA. The inhibition pattern of RA was different from that of dexamethasone, which inhibited both IL-i and LPS effects. In summary, our data show that RA regulates monocyte cytokine expression selectively in response to the particular stimuli. Inhibition of IL-113-induced cytokine expression provides a mechanism that can cx- plain some of the anti-inflammatory effects of RA. J. Leukoc. Biol. 54: 125-132; 1993.