1 Alpha,25-dihydroxyvitamin D3 Suppresses Interleukin-1beta-induced Interleukin-8 Production in Human Whole Blood: an Involvement of Erythrocytes in the Inhibition

Interleukin (IL)-8, which is involved in inflammatory responses, is produced by a variety of cell types, monocytes/macrophages and neutrophils, in response to inflammatory stimuli including lipopolysaccharide, IL-1, and tumor necrosis factor alpha. Here we report the inhibitory effects of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on IL-8 production in human whole blood culture. 1,25(OH)2D3 inhibited only the late phase of the biphasic IL-8 production in lipopolysaccharide-stimulated human whole blood. It also effectively inhibited IL-8 production induced by IL-lbeta compared with that induced by tumor necrosis factor alpha. IL-8 mRNA expression in IL-lbeta-stimulated whole blood was found to require de novo protein synthesis. Although monocytes were found to be mainly responsible for IL-1beta-induced IL-8 production in whole blood, 1,25(OH)2D3 inhibited IL-8 production by isolated mononuclear cells only marginally. The inhibitory effect of 1,25(OH)2D3 on mononuclear cells was restored by adding erythrocytes. These results suggest that erythrocytes play a role in mediating the inhibitory effects of 1,25(OH)2D3 on IL-8 production in IL-1beta-stimulated whole blood.