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      Effect of 1α-Hydroxyvitamin D 3 Treatment on Production of Tumor Necrosis Factor-α by Peripheral Blood Mononuclear Cells and on Serum Concentrations of Soluble Tumor Necrosis Factor Receptors in Hemodialysis Patients

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          The effect of 1,25-dihydroxyvitamin D<sub>3</sub> [1,25-(OH)<sub>2</sub>D<sub>3</sub>] deficiency, as well as of replacement therapy with lα-hydroxyvitamin D<sub>3</sub> [1α-(OH)D<sub>3</sub>], on the production of tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC) and on the serum levels of soluble TNF receptors (sTNFRs) in hemodialysis (HD) patients was investigated. PBMC from HD patients without prior therapy with hydroxylated vitamin D<sub>3</sub> analogs and from normal controls produced similar amounts of TNF-α, either spontaneously or after stimulation with lipopolysaccharide (LPS). After oral administration of 1α-(OH)D<sub>3</sub>, a precursor of 1,25-(OH)<sub>2</sub>D<sub>3</sub>, LPS-induced TNF-α production by PBMC of HD patients was significantly higher than that of HD patients prior to the treatment or of healthy controls. Such treatment did not, however, affect spontaneous TNF-α production by PBMC. Serum concentrations of both soluble TNF receptors [sTNFR-A(p75) and sTNFR-B(p55)] were significantly higher in HD patients than in controls. The ratio of sTNFR-A/sTNFR-B decreased significantly in HD patients following lα-(OH)D<sub>3</sub> therapy. These results suggest that therapy with 1α-hydroxylated vitamin D<sub>3</sub> analogs normally given to HD patients for the management of renal osteodystrophy may also regulate the in vivo activity of TNF-α.

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          Author and article information

          S. Karger AG
          16 December 2008
          : 66
          : 3
          : 262-266
          aDivision of Nephrology, Kaplan Hospital, Rehovot, Israel; bF. Hoffmann-La Roche Ltd., Pharmaceutical Research – New Technologies, Basel, Switzerland; cTeva Pharmaceutical Industries Ltd., Jerusalem, Israel
          187820 Nephron 1994;66:262–266
          © 1994 S. Karger AG, Basel

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          Pages: 5
          Original Paper


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