IL-33 deficiency slows cancer growth but does not protect against cisplatin-induced AKI in mice with cancer

Kameswaran Ravichandran, Sara Holditch, Carolyn N. Brown, Qian Wang, Abdullah Ozkok, Mary C. Weiser-Evans, Raphael Nemenoff, Makoto Miyazaki, Heather Thiessen-Philbrook, Chirag R. Parikh, Danica Ljubanovic, Charles L. Edelstein

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in a 4-wk model of cisplatin-induced AKI in mice with cancer was determined. Mice were injected subcutaneously with murine lung cancer cells. Ten days later, cisplatin (10 mg·kg+¹·wk+¹) was administered weekly for 4 wk. The increase in kidney IL-33 preceded the AKI and tubular injury, suggesting that IL-33 may play a causative role. However, the increase in serum creatinine, blood urea nitrogen, serum neutrophil gelatinase-associated lipoprotein, acute tubular necrosis, and apoptosis scores in the kidney in cisplatin-induced AKI was the same in wild-type and IL-33-deficient mice. There was an increase in kidney expression of pro-inflammatory cytokines CXCL1 and TNF-β, known mediators of cisplatin-induced AKI, in IL-33-deficient mice. Surprisingly, tumor weight, tumor volume, and tumor growth were significantly decreased in IL-33-deficient mice, and the effect of cisplatin on tumors was enhanced in IL-33-deficient mice. As serum IL-33 was increased in cisplatin-induced AKI in mice, it was determined whether serum IL-33 is an early biomarker of AKI in patients undergoing cardiac surgery. Immediate postoperative serum IL-33 concentrations were higher in matched AKI cases compared with non-AKI controls. In conclusion, even though the cancer grows slower in IL-33-deficient mice, the data that IL-33 deficiency does not protect against AKI in a clinically relevant model suggest that IL-33 inhibition may not be useful to attenuate AKI in patients with cancer. However, serum IL-33 may serve as a biomarker of AKI.

Original languageEnglish (US)
Pages (from-to)F356-F366
JournalAmerican Journal of Physiology - Renal Physiology
Volume314
Issue number3
DOIs
StatePublished - Mar 2018
Externally publishedYes

Keywords

  • Cisplatin
  • IL-33
  • Kidney injury

ASJC Scopus subject areas

  • Physiology
  • Urology

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