Deng J, Kohda Y, Chiao H, Wang Y, Hu X, Hewitt S M, Miyaji T, McLeroy P, Nibhanupudy B, Li S, Star R A
Renal Diagnostics and Therapeutics Unit, NIDDK, and Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1268, USA.
Kidney Int. 2001 Dec;60(6):2118-28. doi: 10.1046/j.1523-1755.2001.00043.x.
Acute renal failure (ARF) is caused by ischemic and nephrotoxic insults acting alone or in combination. Anti-inflammatory agents have been shown to decrease renal ischemia-reperfusion and cisplatin-induced injury and leukocyte infiltration. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that inhibits inflammatory and cytotoxic pathways implicated in acute renal injury. Therefore, we sought to determine if IL-10 inhibits acute renal injury.
The effects of IL-10 were studied in mice following cisplatin administration and bilateral renal ischemia-reperfusion, in a rat model of renal transplantation, and in cultured mouse cortical tubule cells.
IL-10 significantly decreased renal injury following cisplatin administration and following renal ischemia/reperfusion. Delay of IL-10 treatment for one hour after cisplatin also significantly inhibited renal damage. IL-10 and alpha-melanocyte stimulating hormone (alpha-MSH) increased recovery following transplantation of a kidney subjected to warm ischemia. To explore the mechanism of action of IL-10, its effects were measured on mediators of leukocyte trafficking and inducible nitric oxide synthase (NOS-II). IL-10 inhibited cisplatin and ischemia-induced increases in mRNA for tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and NOS-II. IL-10 also inhibited staining for markers of apoptosis and cell cycle activity following cisplatin administration, and nitric oxide production in cultured mouse cortical tubules.
IL-10 protects against renal ischemic and cisplatin-induced injury. IL-10 may act, in part, by inhibiting the maladaptive activation of genes that cause leukocyte activation and adhesion, and induction of iNOS.
急性肾衰竭（ARF）由单独或联合作用的缺血性和肾毒性损伤引起。抗炎药物已显示可减少肾缺血再灌注损伤和顺铂诱导的损伤以及白细胞浸润。白细胞介素-10（IL-10）是一种强效抗炎细胞因子，可抑制与急性肾损伤相关的炎症和细胞毒性途径。因此，我们试图确定IL-10是否能抑制急性肾损伤。
在顺铂给药和双侧肾缺血再灌注后的小鼠、肾移植大鼠模型以及培养的小鼠皮质肾小管细胞中研究IL-10的作用。
IL-10可显著减轻顺铂给药后及肾缺血/再灌注后的肾损伤。顺铂给药后1小时延迟给予IL-10治疗也可显著抑制肾损伤。IL-10和α-黑素细胞刺激素（α-MSH）可增加热缺血肾脏移植后的恢复。为探究IL-10的作用机制，检测了其对白细胞迁移介质和诱导型一氧化氮合酶（NOS-II）的影响。IL-10可抑制顺铂和缺血诱导的肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）和NOS-II mRNA的增加。IL-10还可抑制顺铂给药后凋亡和细胞周期活性标志物的染色，以及培养的小鼠皮质肾小管中的一氧化氮生成。
IL-10可保护肾脏免受缺血和顺铂诱导的损伤。IL-10可能部分通过抑制导致白细胞活化和黏附的基因的不适应性激活以及诱导型一氧化氮合酶的诱导而起作用。
