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

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

Izvornik
American journal of physiology. Renal physiology (1931-857X) 314 (2018), 3; F356-F366

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
IL-33 ; cisplatin ; kidney injury

Sažetak
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-α, 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA