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

• Published in: Kidney international Vol. 60; no. 6; pp. 2118 - 2128
• Main Authors: Deng, Jiangping, Kohda, Yukimasa, Chiao, Hsi, Wang, Yuqin, Hu, Xuxhen, Hewitt, Stephen M., Miyaji, Takehiko, Mcleroy, Paul, Nibhanupudy, Bobby, Li, Shujun, Star, Robert A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2001; Nature Publishing; Elsevier Limited
• Subjects: alpha-melanocyte stimulating hormone; alpha-MSH - pharmacology; Animals; Biological and medical sciences; Cells, Cultured; Cisplatin - pharmacology; Drug toxicity and drugs side effects treatment; inflammation; Interleukin-10 - administration & dosage; Interleukin-10 - pharmacology; Ischemia - pathology; ischemia-reperfusion injury; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Kidney Transplantation; Kidney Tubules - cytology; Kidney Tubules - drug effects; leukocytes; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; nitric oxide synthase; Pharmacology. Drug treatments; Preservation, Biological; Rats; Rats, Inbred Lew; Renal Circulation; renal transplantation; Reperfusion Injury - pathology; Time Factors; Toxicity: urogenital system; ischemia-reperfusion injury; leukocytes; nitric oxide synthase; inflammation; renal transplantation; alpha-melanocyte stimulating hormone; Kidney disease; Urinary system disease; Toxicity; Acute; Cytokine; Exploration; Lamb; Cisplatin; Chemotherapy; Vertebrata; Mammalia; Treatment; Ischemia; Animal; Renal failure; Interleukin 10; Sheep; Artiodactyla; Ungulata; Platinum II Complexes
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.2001.00043.x

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