Korean J Intern Med.  2011 Jun;26(2):187-194. 10.3904/kjim.2011.26.2.187.

Role of IL-1alpha in Cisplatin-Induced Acute Renal Failure in Mice

• Lee JW
• Nam WJ
• Han MJ
• Shin JH
• Kim JG
• Kim SH
• Kim HR
• Oh DJ

• KMID: 1776591
• DOI: http://doi.org/10.3904/kjim.2011.26.2.187

Abstract

BACKGROUND/AIMS
For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-1alpha. We thus asked whether IL-1alpha deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice.
METHODS
Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-1alpha was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-1alpha -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-1alpha -/- mice.
RESULTS
Compared with vehicle-treated mice, renal IL-1alpha increased in cisplatin-treated wild-type mice beginning on day 1. IL-1alpha -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-1alpha -/- mice.
CONCLUSIONS
Mice deficient in IL-1alpha are protected against cisplatin-induced ARF. The lack of IL-1alpha may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-1alpha -/- mice in cisplatin-induced ARF merits further study.

Keyword

Cisplatin; Interleukin-1alpha; Acute kidney injury

MeSH Terms

Acute Kidney Injury/chemically induced/*immunology/pathology/physiopathology/prevention & control
Animals
Antigens, CD11b/analysis
Apoptosis
Biological Markers/blood
Blood Urea Nitrogen
*Cisplatin
Creatinine/blood
Disease Models, Animal
Fluorescent Antibody Technique
Integrin alpha2/analysis
Interleukin-1alpha/deficiency/genetics/*metabolism
Kidney/*immunology/pathology/physiopathology
Killer Cells, Natural/immunology
Macrophages/immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Natural Killer T-Cells/immunology
Necrosis
Neutrophil Infiltration
Time Factors