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

J. Deng, Y. Kohda, H. Chiao, Y. Wang, X. Hu, S. M. Hewitt, T. Miyaji, P. McLeroy, B. Nibhanupudy, S. Li, R. A. Star

Research output: Contribution to journalArticle

288 Scopus citations

Abstract

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 α-melanocyte stimulating hormone (α-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-α (TNF-α), 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.

Original languageEnglish (US)
Pages (from-to)2118-2128
Number of pages11
JournalKidney international
Volume60
Issue number6
DOIs
StatePublished - Jan 1 2001

Keywords

  • Alpha-melanocyte stimulating hormone
  • Inflammation
  • Ischemia-reperfusion injury
  • Leukocytes
  • Nitric oxide synthase
  • Renal transplantation

ASJC Scopus subject areas

  • Nephrology

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    Deng, J., Kohda, Y., Chiao, H., Wang, Y., Hu, X., Hewitt, S. M., Miyaji, T., McLeroy, P., Nibhanupudy, B., Li, S., & Star, R. A. (2001). Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney international, 60(6), 2118-2128. https://doi.org/10.1046/j.1523-1755.2001.00043.x