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

282 Citations (Scopus)

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 - 2001

Fingerprint

Acute Kidney Injury
Interleukin-10
Cisplatin
Nitric Oxide Synthase Type II
Kidney
Ischemia
Reperfusion
Leukocytes
Kidney Transplantation
Wounds and Injuries
Anti-Inflammatory Agents
Melanocyte-Stimulating Hormones
Warm Ischemia
Intercellular Adhesion Molecule-1
Transcriptional Activation
Cell Cycle
Nitric Oxide
Tumor Necrosis Factor-alpha
Apoptosis
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. / Deng, J.; Kohda, Y.; Chiao, H.; Wang, Y.; Hu, X.; Hewitt, S. M.; Miyaji, T.; McLeroy, P.; Nibhanupudy, B.; Li, S.; Star, R. A.

In: Kidney International, Vol. 60, No. 6, 2001, p. 2118-2128.

Research output: Contribution to journalArticle

Deng, J, Kohda, Y, Chiao, H, Wang, Y, Hu, X, Hewitt, SM, Miyaji, T, McLeroy, P, Nibhanupudy, B, Li, S & Star, RA 2001, 'Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury', Kidney International, vol. 60, no. 6, pp. 2118-2128. https://doi.org/10.1046/j.1523-1755.2001.00043.x
Deng, J. ; Kohda, Y. ; Chiao, H. ; Wang, Y. ; Hu, X. ; Hewitt, S. M. ; Miyaji, T. ; McLeroy, P. ; Nibhanupudy, B. ; Li, S. ; Star, R. A. / Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. In: Kidney International. 2001 ; Vol. 60, No. 6. pp. 2118-2128.
@article{5a8e60c98b5943eca8b1a28cd466a34c,
title = "Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury",
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.",
keywords = "Alpha-melanocyte stimulating hormone, Inflammation, Ischemia-reperfusion injury, Leukocytes, Nitric oxide synthase, Renal transplantation",
author = "J. Deng and Y. Kohda and H. Chiao and Y. Wang and X. Hu and Hewitt, {S. M.} and T. Miyaji and P. McLeroy and B. Nibhanupudy and S. Li and Star, {R. A.}",
year = "2001",
doi = "10.1046/j.1523-1755.2001.00043.x",
language = "English (US)",
volume = "60",
pages = "2118--2128",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury

AU - Deng, J.

AU - Kohda, Y.

AU - Chiao, H.

AU - Wang, Y.

AU - Hu, X.

AU - Hewitt, S. M.

AU - Miyaji, T.

AU - McLeroy, P.

AU - Nibhanupudy, B.

AU - Li, S.

AU - Star, R. A.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Alpha-melanocyte stimulating hormone

KW - Inflammation

KW - Ischemia-reperfusion injury

KW - Leukocytes

KW - Nitric oxide synthase

KW - Renal transplantation

UR - http://www.scopus.com/inward/record.url?scp=0035176820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035176820&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2001.00043.x

DO - 10.1046/j.1523-1755.2001.00043.x

M3 - Article

C2 - 11737586

AN - SCOPUS:0035176820

VL - 60

SP - 2118

EP - 2128

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 6

ER -