title: Effect of 1 alpha-hydroxyvitamin D3 treatment on production of tumor necrosis factor-alpha by peripheral blood mononuclear cells and on serum concentrations of soluble tumor necrosis factor receptors in hemodialysis patients.
abstract: The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] deficiency, as well as of replacement therapy with 1 alpha-hydroxyvitamin D3[1 alpha-(OH)D3], on the production of tumor necrosis factor-alpha (TNF-alpha) 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 D3 analogs and from normal controls produced similar amounts of TNF-alpha, either spontaneously or after stimulation with lipopolysaccharide (LPS). After oral administration of 1 alpha-(OH)D3, a precursor of 1,25-(OH)2D3, LPS-induced TNF-alpha 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-alpha 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 1 alpha-(OH)D3 therapy. These results suggest that therapy with 1 alpha-hydroxylated vitamin D3 analogs normally given to HD patients for the management of renal osteodystrophy may also regulate the in vivo activity of TNF-alpha.
authors.affiliation: Division of Nephrology, Kaplan Hospital, Rehovot, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Haran
authors.forename: S
authors.initials: S
authors.lastname: Gurwicz
authors.forename: H
authors.initials: H
authors.lastname: Gallati
authors.forename: B
authors.initials: B
authors.lastname: Shalita
authors.forename: Y
authors.initials: Y
authors.lastname: Bar-Khayim
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism*
chemical_list: D006887:Hydroxycholecalciferols; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C008088:alfacalcidol