Apoptotic cell-free DNA promotes inflammation in haemodialysis patients

Nephrol Dial Transplant. 2012 Mar;27(3):902-5. doi: 10.1093/ndt/gfr695. Epub 2011 Dec 13.

Abstract

Background: A proinflammatory environment characterized by the continuous activation of the innate immune system is thought to contribute to the markedly elevated mortality in haemodialysis (HD) patients with end-stage renal disease (ESRD). The presence of circulating cell-free DNA (cfDNA) has been demonstrated as biomarker in many pathologies.

Methods: We evaluated the occurrence of cfDNA in HD patients and its functional relevance for innate immunity and inflammation.

Results: Here, we found that cfDNA was enhanced in the plasma of ESRD patients after HD compared to healthy controls. Functionally, cfDNA selectively stimulated the production of the proinflammatory cytokine interleukin (IL)-6 by human monocytes, whereas tumour necrosis factor-α or IL-10 was not induced. Conversely, plasma from HD patients, but not from healthy controls or DNase I-treated HD plasma, induced IL-6 production from monocytes.

Conclusion: We provide the first evidence that cfDNA has selective immunostimulatory effects on human monocytes. This process may contribute to the proinflammatory milieu observed in HD patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Biomarkers / blood*
  • Case-Control Studies
  • DNA / blood*
  • Humans
  • Immunity, Innate
  • Inflammation / blood
  • Inflammation / etiology*
  • Interleukin-1 / blood
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / mortality
  • Monocytes / cytology
  • Monocytes / metabolism
  • Renal Dialysis / adverse effects*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Biomarkers
  • Interleukin-1
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • DNA