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

Background Ischemia followed by reperfusion is a common clinical event asso ciated with a pro-inflammatory response leading to organ dysfunction, The a im of the present study is to evaluate the interplay between this pro-infla mmatory response and apoptosis. We investigated the role of the pro-inflamm atory mediator tumor necrosis factor-alpha (TNF-cu) and the anti-inflammato ry mediator interleukin-10 (IL-10) in inflammation and apoptosis after rena l ischemia reperfusion. Methods. Male Swiss mice were subjected to 45 min of ischemia followed by r eperfusion and subsequently administered neutralizing Abs against either TN F-alpha (TN3), IL-10 (JES5-2A5) or control, Results. After 1 day of reperfusion, anti-TNF-alpha treatment reduced where as anti-IL-10 treatment exacerbated postischemic renal injury, inflammation , and, to a lesser extent, apoptosis as measured by changes in blood urea n itrogen content, immunohistologically detectable renal TNF-alpha protein an d neutrophils, histological integrity of renal parenchyma, and DNA ladder f ormation. Furthermore, anti-IL-10 treatment enhanced major histocompatibili ty complex class I and II expression at day 7 as measured by enzyme immunoa ssay and immunohistology. Conclusions. These data indicate that the extent of reperfusion-induced apo ptosis is modulated by the inflammatory response, during which locally prod uced TNF-alpha plays a significant role in the development of tissue injury . Subsequently, this pro-inflammatory reaction is followed by endogenous pr oduction of the anti-inflammatory cytokine IL-10, which serves as a physiol ogical counterbalance to the effects of TNF-alpha, These novel pathophysiol ogical insights may provide new basis for the development of tools for limi ting ischemia and reperfusion injury.