title: Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury.
abstract: 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.
authors: Department of General Surgery of the University of Maastricht, The Netherlands. w.buurman@ah.unimaas.nl
authors: M A
authors: MA
authors: Daemen
authors: M W
authors: MW
authors: van de Ven
authors: E
authors: E
authors: Heineman
authors: W A
authors: WA
authors: Buurman
mesh_terms: D000818:Animals; D017209:Apoptosis; D007249:Inflammation / Q000209:etiology; D016753:Interleukin-10 / Q000502:physiology*; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D015427:Reperfusion Injury / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10