Amelioration of renal ischemia-reperfusion injury by inhibition of IL-6 production in the poloxamer 407-induced mouse model of hyperlipidemia.
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.
Sharyo
Satoru
S
Department of Veterinary Pharmacology, University of Miyazaki, Japan.
Kumagai
Kazuyoshi
K
Yokota-Ikeda
Naoko
N
Ito
Katsuaki
K
Ikeda
Masahiro
M
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D006949:Hyperlipidemias / Q000139:chemically induced / Q000503:physiopathology*; D007202:Indicators and Reagents; D015850:Interleukin-6 / Q000096:biosynthesis; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020442:Poloxamer; D015427:Reperfusion Injury / Q000188:drug therapy*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013501:Surface-Active Agents; D000093242:Interleukin-6 Inhibitors
D001057:Apolipoproteins E; D003404:Creatinine; D007202:Indicators and Reagents; D015850:Interleukin-6; D020442:Poloxamer; D013501:Surface-Active Agents; D000093242:Interleukin-6 Inhibitors