Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury

Transplantation. 1999 Mar 27;67(6):792-800. doi: 10.1097/00007890-199903270-00003.


Background: Ischemia followed by reperfusion is a common clinical event associated with a pro-inflammatory response leading to organ dysfunction. The aim of the present study is to evaluate the interplay between this pro-inflammatory response and apoptosis. We investigated the role of the pro-inflammatory mediator tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory mediator interleukin-10 (IL-10) in inflammation and apoptosis after renal ischemia reperfusion.

Methods: Male Swiss mice were subjected to 45 min of ischemia followed by reperfusion and subsequently administered neutralizing Abs against either TNF-alpha (TN3), IL-10 (JES5-2A5) or control.

Results: After 1 day of reperfusion, anti-TNF-alpha treatment reduced whereas anti-IL-10 treatment exacerbated postischemic renal injury, inflammation, and, to a lesser extent, apoptosis as measured by changes in blood urea nitrogen content, immunohistologically detectable renal TNF-alpha protein and neutrophils, histological integrity of renal parenchyma, and DNA ladder formation. Furthermore, anti-IL-10 treatment enhanced major histocompatibility complex class I and II expression at day 7 as measured by enzyme immunoassay and immunohistology.

Conclusions: These data indicate that the extent of reperfusion-induced apoptosis is modulated by the inflammatory response, during which locally produced TNF-alpha plays a significant role in the development of tissue injury. Subsequently, this pro-inflammatory reaction is followed by endogenous production of the anti-inflammatory cytokine IL-10, which serves as a physiological counterbalance to the effects of TNF-alpha. These novel pathophysiological insights may provide new basis for the development of tools for limiting ischemia and reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Inflammation / etiology
  • Interleukin-10 / physiology*
  • Ischemia / complications*
  • Kidney / blood supply*
  • Male
  • Mice
  • Reperfusion Injury / etiology*
  • Tumor Necrosis Factor-alpha / physiology*


  • Tumor Necrosis Factor-alpha
  • Interleukin-10