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-inflammatory effects in vivo, the basis of which is not clearly understood. 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-1 beta (IL-1 beta), IL-6, and IL-8 mRNAs depending on the inducing stimulus. While phorbol myristate acetate-induced IL-1 beta and IL-8 mRNA expression was increased by RA (IL-6 could not be induced by this pathway in monocytes), IL-1 beta-induced expression of IL-1 beta 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 required a longer preincubation (> 72 h) of monocytes with RA. IL-1-induced de novo synthesis of IL-6 protein and secretion of biologically active IL-6 were also inhibited by RA. The inhibition pattern of RA was different from that of dexamethasone, which inhibited both IL-1 and LPS effects. In summary, our data show that RA regulates monocyte cytokine expression selectively in response to the particular stimuli. Inhibition of IL-1 beta-induced cytokine expression provides a mechanism that can explain some of the anti-inflammatory effects of RA.