Early renal ischemia-reperfusion injury in humans is dominated by IL-6 release from the allograft

Am J Transplant. 2009 Jul;9(7):1574-84. doi: 10.1111/j.1600-6143.2009.02675.x. Epub 2009 May 20.


The pathophysiology of ischemia/reperfusion (I/R) injury is complex, and current knowledge of I/R injury in humans is incomplete. In the present study, human living-donor kidney transplantation was used as a highly reproducible model to systematically study various processes potentially involved in early I/R injury. Unique, direct measurements of arteriovenous concentration differences over the kidney revealed massive release of interleukin (IL)-6 in the first 30 minutes of graft reperfusion and a modest release of IL-8. Among the assessed markers of oxidative and nitrosative stress, only 15(S)-8-iso-PGF(2alpha) was released. When assessing cell activation, release of prothrombin factor 1 + 2 indicated thrombocyte activation, whereas there was no release of markers for endothelial activation or neutrophil activation. Common complement activation complex sC5b-9 was not released into the bloodstream, but was released into urine rapidly after reperfusion. To investigate whether IL-6 plays a modulating role in I/R injury, a mouse experiment of renal I/R injury was performed. Neutralizing anti-IL-6 antibody treatment considerably worsened kidney function. In conclusion, this study shows that renal I/R in humans is dominated by local IL-6 release. Neutralization of IL-6 in mice resulted in a significant aggravation of renal I/R injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Complement Membrane Attack Complex / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Kidney / blood supply*
  • Kidney / injuries*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology
  • Kidney Transplantation / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Neutralization Tests
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reperfusion Injury / blood
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / immunology
  • Transplantation, Homologous


  • Complement Membrane Attack Complex
  • IL6 protein, human
  • Interleukin-6
  • RNA, Messenger