Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury.
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.
Deng
J
J
Renal Diagnostics and Therapeutics Unit, NIDDK, and Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1268, USA.
Kohda
Y
Y
Chiao
H
H
Wang
Y
Y
Hu
X
X
Hewitt
S M
SM
Miyaji
T
T
McLeroy
P
P
Nibhanupudy
B
B
Li
S
S
Star
R A
RA
D000818:Animals; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D016753:Interleukin-10 / Q000008:administration & dosage / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011309:Preservation, Biological; D051381:Rats; D011917:Rats, Inbred Lew; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology; D013997:Time Factors; D000521:alpha-MSH / Q000494:pharmacology
D016753:Interleukin-10; D000521:alpha-MSH; D002945:Cisplatin