28
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Zinc modulates mononuclear cellular calcitriol metabolism in peritoneal dialysis patients

      , , ,
      Kidney International
      Springer Nature

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Zinc has long been known to play a role in maintaining immunologic function. Hypozincemia, however, is common in patients with end-stage renal disease (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). We previously demonstrated that zinc depletion limits the ability of animals to achieve maximum circulating calcitriol levels in response to the stress of calcium or phosphorus depletion. It was unclear, however, whether changes in the circulating levels of calcitriol in these settings was associated with a direct effect on renal 1-alpha hydroxylase activity, or whether the zinc dependence of the stimulated calcitriol response involved an integrated systemic response in intact animals. In addition it was unclear whether circulating zinc levels or zinc nutritional status modified calcitriol metabolism in humans. To better understand the role zinc plays in the immune response in patients with ESRD, we studied IL-1, calcitriol and tumor necrosis factor-alpha production by mononuclear cells from blood and peritoneal effluents of 22 patients with ESRD treated with CAPD. Macrophages from peritoneal effluents and peripheral blood mononuclear cells were isolated and pulsed with phytohemagglutinin in medium to which different concentrations of zinc chloride, copper chloride, and carbonyl cyanide p-(trifluoromethoxy)-phenyl-hydrazone (FCCP), an inhibitor of mitochondrial function were added. Supernatant interleukin-1, calcitriol, and tumor necrosis factor-alpha levels were subsequently measured. We demonstrated a zinc concentration dependent increase in stimulated IL-1 alpha and -beta, and TNF-alpha release in both peripheral mononuclear cells and peritoneal macrophages from patients with ESRD treated with CAPD. The effect is zinc specific, as it is not reproduced by copper or chloride supplementation. A zinc concentration dependent increase in peritoneal macrophage calcitriol release was also noted. FCCP blocked the cellular production of IL-1 alpha, IL-1 beta, and TNF-alpha, but had little effect on zinc-induced stimulated mononuclear cell supernatant calcitriol levels. The different shape of the zinc dose response curve, and the lack of correlation between paired IL-1 and calcitriol supernatant levels suggests the effect of zinc on mononuclear cellular cytokine and calcitriol production is mediated through different pathways.

          Related collections

          Author and article information

          Journal
          Kidney International
          Kidney International
          Springer Nature
          00852538
          May 1996
          May 1996
          : 49
          : 5
          : 1407-1412
          Article
          10.1038/ki.1996.198
          8731107
          86facc6f-9826-4b86-83fc-13b142cbb60c
          © 1996

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

          History

          Comments

          Comment on this article