Innate immunity in hemodialysis and continuous ambulatory peritoneal dialysis patients: Impaired cytokine synthetic response to ex-vivo stimuli in mononuclear cells

  • SHIBUYA Asuka
    Department of Medicine IV, Tokyo Women's Medical University
  • ANDO Minoru
    Division of Nephrology, Tokyo Metropolitan Komagome Hospital
  • TSUCHIYA Ken
    Department of Medicine IV, Tokyo Women's Medical University
  • AKIBA Takashi
    Department of Blood Purification, Tokyo Women's Medical University
  • NIHEI Hiroshi
    Department of Medicine IV, Tokyo Women's Medical University

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Other Title
  • 連続携行式腹膜透析患者と血液透析患者における自然免疫能の比較―単核球の外因刺激に対するサイトカイン産生反応からみた検討
  • Impaired cytokine synthetic response to <i>ex-vivo</i> stimuli in mononuclear cells
  • 単核球の外因刺激に対するサイトカイン産生反応からみた検討

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Abstract

Dialysis patients are weak in immune host defense, which is associated with their high morbidity of infection. Polymorphonuclear leukocytes (PMNLs) and mononuclear cells play a key role in innate host defense. PMNLs and monocytes have bactericidal activity through the process of phagocytosis. Monocytes and lymphocytes contribute to the development of innate immunity by their cytokine actions. We studied the intracellular cytokine syntheses in response to ex-vivo stimuli, which may reflect the potential reactivity of immune cells in cytokine syntheses when pathogens invade humans. Furthermore, phagocytic activity was assessed in granulocytes and monocytes. Twenty HD, 15 CAPD, and 10 age-matched controls were enrolled in this study. One milliliter of whole blood from each subject was incubated with lipopolysaccharides (LPS) or mitogens for 4 hours at 3T°C. Monoclonal antibodies to CD14+ and CD4+ were used for identifying monocytes and helper T cells, respectively. Intracellular cytokines were stained using FASTIMMUNE® staining kits. Interleukin-1β and TNF-α syntheses were examined in monocytes, which are the most important early-response cytokines in innate immunity. IFN-γ and IL-4 syntheses were examined in helper T cells to observe their polarization into Th1 and Th2 cells. IFN-γ is a key factor in establishing innate immunity. The percentage of cells that stained positive for each cytokine was analyzed using a flow cytometer.<br>The following results were obtained: 1) In CAPD patients, IL-1β and TNF-α response to LPS in monocytes were significantly reduced, as compared to other subjects. Polarization of helper T cells was reduced, resulting in a significant decrease in Th1 cells. 2) In HD patients, monokine responses were not altered, but polarization of helper T cells was skewed toward a Th1 type. Phagocytic activities were not impaired in both dialysis groups. In conclusion, mononuclear cells from CAPD patients have the potential to exhibit failure of a cytokine response to ex-vivo stimuli in terms of innate immunity.

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