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.
Subject(s)
Hydroxycholecalciferols/therapeutic use , Leukocytes, Mononuclear/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Renal Dialysis , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/metabolism , Administration, Oral , Adult , Aged , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/drug therapy , Kidney Failure, Chronic/therapy , Leukocytes, Mononuclear/drug effects , Male , Middle AgedABSTRACT
Two soluble tumor necrosis factor receptors (sTNFRs) were detected in the plasma of patients with different degrees of chronic renal failure (CRF) and of long-term hemodialysis (HD) patients. In uremic undialyzed patients, plasma levels of both sTNFRs increased progressively with declining renal function. A linear correlation was found between sTNFR plasma levels and plasma creatinine concentration. sTNFR levels in end-stage uremic patients shortly before commencement of first HD treatment were approximately tenfold higher than in normal subjects. Long-term HD patients showed a further increase in plasma sTNFRs. The origin of sTNFRs, as well as their physiological role remains to be elucidated.
Subject(s)
Kidney Failure, Chronic/blood , Receptors, Cell Surface/metabolism , Adult , Aged , Female , Humans , Immunoassay , Kidney/physiopathology , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Osmolar Concentration , Receptors, Tumor Necrosis Factor , Renal Dialysis , Solubility , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A 43-year-old man with hairy-cell leukemia and marked splenomegaly developed severe hypophosphatemia which improved after splenectomy. Since splenic tissue phosphorus was significantly elevated, and since serum phosphorus returned to normal levels immediately after the operation, it is postulated that excessive uptake of phosphorus by the rapidly dividing leukemic cells might have caused the transient decrease in serum phosphorus.
