Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury
Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury
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DOI：
10.1046/j.1523-1755.2001.00043.x
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发表时间：
2001-12-01
影响因子：
19.6
通讯作者：
Star, RA
中科院分区：
文献类型：
--
作者：
Deng, JP;Kohda, Y;Star, RA
背景。急性肾功能衰竭（ARF）是由单独或联合作用的缺血性和肾毒性损伤引起的。抗炎药已被证明可以减少肾缺血再灌注和顺铂诱导的损伤和白细胞浸润。白细胞介素-10 （IL-10）是一种有效的抗炎细胞因子，可抑制与急性肾损伤有关的炎症和细胞毒性途径。因此，我们试图确定IL-10是否抑制急性肾损伤。研究了IL-10对小鼠顺铂给药后双侧肾缺血再灌注、大鼠肾移植模型和培养小鼠皮质小管细胞的影响。IL-10显著降低顺铂给药后和肾缺血再灌注后的肾损伤。顺铂治疗后延迟IL-10治疗1小时也能显著抑制肾损害。IL-10和α -促黑素细胞激素（α -MSH）增加热缺血肾移植后的恢复。为了探讨IL-10的作用机制，我们检测了IL-10对白细胞转运介质和诱导型一氧化氮合酶（NOS-II）的影响。IL-10抑制顺铂和缺血诱导的肿瘤坏死因子-a （tnf - α）、细胞间粘附分子-1 （ICAM-1）和NOS-II mRNA的升高。IL-10还能抑制小鼠皮质小管中顺铂给药后细胞凋亡和细胞周期活性标记物的染色，以及一氧化氮的产生。IL-10对肾缺血和顺铂诱导的损伤有保护作用。在某种程度上，IL-10可能通过抑制引起白细胞活化和粘附的基因的不适应激活以及诱导iNOS起作用。
Background. 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.Methods. 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.Results. 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-a (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.Conclusions. 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.