1α,25-DIHYDROXYVITAMIN D3SUPPRESSES INTERLEUKIN-1β-INDUCED INTERLEUKIN-8 IN HUMAN WHOLE BLOOD: AN INVOLVEMENT OF ERYTHROCYTES IN THE INHIBITION

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Abstract
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 lipopolysaccha ride, IL-1, and tumor necrosis factor α. Here we report the inhibitory effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on IL-8 production-dates printpubdate="05/03/02" in human whole blood culture. 1,25(OH)2D3 inhibited only the late phase of the biphasic IL-8 production-dates printpubdate="05/03/02" in lipopolysaccharide-stimulated human whole blood. It also effectively inhibited IL-8 production-dates printpubdate="05/03/02" induced by IL-1β compared with that induced by tumor necrosis factor α. IL-8 mRNA expression in IL-1β-stimulated whole blood was found to require de novo protein synthesis. Although monocytes were found to be mainly responsible for IL-1β-induced IL-8 production-dates printpubdate="05/03/02" in whole blood, 1,25(OH)2D3 inhibited IL-8 production-dates printpubdate="05/03/02" 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-dates printpubdate="05/03/02" in IL-1β-stimulated whole blood.