Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury

Kidney Int. 2001 Dec;60(6):2118-28. doi: 10.1046/j.1523-1755.2001.00043.x.


Background: Acute renal failure (ARF) is caused by ischemic and nephrotoxic insults acting alone or in combination. Anti-inflammatory agents have been shown to decrease renal ischemia-reperfusion and cisplatin-induced injury and leukocyte infiltration. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits inflammatory and cytotoxic pathways implicated in acute renal injury. Therefore, we sought to determine if IL-10 inhibits acute renal injury.

Methods: The effects of IL-10 were studied in mice following cisplatin administration and bilateral renal ischemia-reperfusion, in a rat model of renal transplantation, and in cultured mouse cortical tubule cells.

Results: IL-10 significantly decreased renal injury following cisplatin administration and following renal ischemia/reperfusion. Delay of IL-10 treatment for one hour after cisplatin also significantly inhibited renal damage. IL-10 and alpha-melanocyte stimulating hormone (alpha-MSH) increased recovery following transplantation of a kidney subjected to warm ischemia. To explore the mechanism of action of IL-10, its effects were measured on mediators of leukocyte trafficking and inducible nitric oxide synthase (NOS-II). IL-10 inhibited cisplatin and ischemia-induced increases in mRNA for tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and NOS-II. IL-10 also inhibited staining for markers of apoptosis and cell cycle activity following cisplatin administration, and nitric oxide production in cultured mouse cortical tubules.

Conclusions: IL-10 protects against renal ischemic and cisplatin-induced injury. IL-10 may act, in part, by inhibiting the maladaptive activation of genes that cause leukocyte activation and adhesion, and induction of iNOS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cisplatin / pharmacology*
  • Interleukin-10 / administration & dosage
  • Interleukin-10 / pharmacology*
  • Ischemia / pathology*
  • Kidney / drug effects*
  • Kidney / pathology*
  • Kidney / physiopathology
  • Kidney Transplantation
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Preservation, Biological
  • Rats
  • Rats, Inbred Lew
  • Renal Circulation*
  • Reperfusion Injury / pathology
  • Time Factors
  • alpha-MSH / pharmacology


  • Interleukin-10
  • alpha-MSH
  • Cisplatin