TY - JOUR
T1 - IL-33 deficiency slows cancer growth but does not protect against cisplatin-induced AKI in mice with cancer
AU - Ravichandran, Kameswaran
AU - Holditch, Sara
AU - Brown, Carolyn N.
AU - Wang, Qian
AU - Ozkok, Abdullah
AU - Weiser-Evans, Mary C.
AU - Nemenoff, Raphael
AU - Miyazaki, Makoto
AU - Thiessen-Philbrook, Heather
AU - Parikh, Chirag R.
AU - Ljubanovic, Danica
AU - Edelstein, Charles L.
N1 - Funding Information:
This work was supported by Veterans Affairs Merit Award 1I01BX001737-01A1 (to C. Edelstein); National Institutes of Health Grants CA-162226, CA-198619, and CA-058187 (to R. Nemenoff); HL-121877 and HL-123616 (to M. Weiser-Evans); and RO1 HL-85757 (to C. Parikh).
Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Cisplatin
KW - IL-33
KW - Kidney injury
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U2 - 10.1152/ajprenal.00040.2017
DO - 10.1152/ajprenal.00040.2017
M3 - Article
C2 - 29070568
AN - SCOPUS:85043576241
SN - 0363-6127
VL - 314
SP - F356-F366
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 3
ER -