Amelioration of Renal Ischemia–Reperfusion Injury by Inhibition of IL-6 Production in the Poloxamer 407–Induced Mouse Model of Hyperlipidemia

• Published in: Journal of Pharmacological Sciences 2009, Vol.110(1), pp.47-54
• Main Authors: Sharyo, Satoru, Kumagai, Kazuyoshi, Yokota-Ikeda, Naoko, Ito, Katsuaki, Ikeda, Masahiro
• Format: Article
• Language: English
• Subjects: angiopoietin-like 3–deficient mouse; Animals; apolipoprotein E–knockout mouse; Apolipoproteins E - genetics; Blood Urea Nitrogen; Creatinine - blood; Hyperlipidemias - chemically induced; Hyperlipidemias - physiopathology; IL-6; Indicators and Reagents; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - biosynthesis; Kidney Diseases - drug therapy; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Poloxamer; poloxamer 407; renal ischemia–reperfusion injury; Reperfusion Injury - drug therapy; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Surface-Active Agents
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.08283FP

It is largely unknown whether hyperlipidemia is involved in the pathobiology of renal ischemia–reperfusion (I/R) injury that is an important cause of acute kidney injury. Here we studied the effect of experimental dyslipidemia on renal I/R injury. Renal I/R injury was less severe in hyperlipidemic mice treated with poloxamer 407 than in the control mice. Cytokine analyses revealed decreased levels of renal and serum IL-6 in the hyperlipidemic mice after renal I/R. Protection from renal I/R injury in the hyperlipidemic mice was diminished by administration of recombinant IL-6. Concanavalin A–induced IL-6 release from cultured splenocytes derived from the hyperlipidemic mice was lower than that from splenocytes of normal mice. In hypercholesterolemic apolipoprotein E–knockout mice, in which renal I/R injury is less severe than in control mice, renal I/R–induced IL-6 production was also less than that in controls. In angiopoietin-like 3–deficient mice, which were hypolipidemic, renal dysfunction and renal IL-6 level after I/R were similar to those of control mice. Our data indicate that the presence of experimental hyperlipidemia may be associated with a decreased risk of renal I/R injury, possibly mediated by reduced renal IL-6 production after the insult and extend the notion that an anti-IL6 agent would be useful for the treatment of acute kidney injury.