EFFECT OF 1-ALPHA-HYDROXYVITAMIN D-3 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

The effect of 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] deficiency, as well as of replacement therapy with 1 alpha-hydroxyvitamin D-3 [1 a lpha-(OH)D-3], on the production of tumor necrosis factor-alpha (TNF-a lpha) by peripheral blood mononuclear cells (PBMC) and on the serum le vels of soluble TNF receptors (sTNFRs) in hemodialysis (HD) patients w as investigated. PBMC from HD patients without prior therapy with hydr oxylated vitamin D-3 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)D-3 , a precursor of 1,25-(OH)(2)D-3, 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 conce ntrations 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)D-3 therapy. These results suggest that therapy with 1 alph a-hydroxylated vitamin D-3 analogs normally given to HD patients for t he management of renal osteodystrophy may also regulate the in vivo ac tivity of TNF-alpha.