Interleukin-6 deficiency accelerates cisplatin-induced acute renal failure but not systemic injury

Interleukin-6 plays a protective role in development of cisplatin-induced acute renal failure through upregulation of anti-oxidative stress factors

“…In contrast, increase of SOD activity in serum obtained from IL-6 −/− mice might lead to a reduction of ROS systemically. These results are consistent with our previous data showing that IL-6 deficiency accelerates acute renal dysfunction, whereas the survival rate of IL-6 −/− mice was better than that of WT mice after cisplatin administration (Mitazaki et al, 2009). …”

“…We previously reported that renal dysfunction accompanied by IL-6 induction was observed in a mouse bilateral hind limb ischemia-reperfusion model and that predominant progression of renal injury in IL-6 knockout (IL-6 −/− ) mice was also observed at an early stage . We have also reported that IL-6 deficiency accelerates cisplatin-induced acute renal failure, indicating that IL-6 plays a protective role in the progress of cisplatininduced acute renal failure at the early stage (Mitazaki et al, 2009). Significant expression of inflammation-and apoptosis-related genes in the kidneys was also observed in IL-6 −/− mice compared to that in wildtype (WT) mice.…”

“…Specially, Bax expression was thought to contribute to the progress of cisplatin-induced acute renal failure in IL-6 −/− mice. IL-6 produced in renal tubular cells is thought to prevent progression of acute renal failure at the early stage (Mitazaki et al, 2009). In the present study, we examined downstream signals of IL-6 and oxidative stress factors, and observed significant phosphorylation of ERK, strong expression of 4-HNE and cox-2, and decrease of SOD activities in the kidney obtained from IL-6 −/− mice after cisplatin administration.…”

“…Mice were given either cisplatin (30 mg/ kg) or saline (control) intraperitoneally. This single dose of cisplatin produced severe renal failure and different survival rates in WT and IL-6 −/− mice (Mitazaki et al, 2009). Under deep anesthesia with Nembutal (Dainippon Sumitomo Pharma., Japan), blood samples were collected via cardiac puncture and kidneys were removed at 24 h and 72 h after cisplatin administration.…”

The nucleotide excision repair protein XPC is essential for bulky DNA adducts to promote interleukin-6 expression via the activation of p38-SAPK

“…46,47 IL-6 might also protect against CDDP-induced neuropathies and kidney injury. 48,49 In contrast to recent studies that have demonstrated activation of p38-SAPK in mouse breast tumors in response to CDDP, 50 we failed to detect increased p38-SAPK phosphorylation in total homogenates from CDDP-treated lungs (data not shown). However, we note that instillated CDDP will only deposit in parts of the lung at the air-liquid interface, and hence more refined methods, such as immunofluorescence studies, are needed to monitor p38-SAPK phosphorylation in vivo.…”