Muhetaer Gulimire, Takeuchi Hironori, Akizuki Sogo, Iwamoto Hitoshi, Shimazu Motohide, Unezaki Sakae, Hirano Toshihiko
Department of 5th Surgery, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan; †Department of Surgery, Uygur Autonomous Region People's Hospital, Xinjiang Uyghur Autonomous Region, China.
‡ Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences , Tokyo , Japan.
Cell Med. 2012 May 14;3(1-3):75-80. doi: 10.3727/215517912X639423. eCollection 2012 Jan.
Lymphocyte sensitivity to endogenous glucocorticoid cortisol could be a biological marker for safe reduction and withdrawal of steroids in renal transplant recipients. We compared peripheral lymphocyte sensitivity with cortisol between transplant recipients treated with tacrolimus (Tac) and those treated with cyclosporine. The suppressive efficacies of cortisol against T-cell mitogen-stimulated proliferation of peripheral lymphocytes were investigated in 44 renal transplant patients, who either had reduced or been withdrawn from steroid treatment. Twenty of the 44 patients were treated with Tac, and the other 24 patients were treated with cyclosporine A (CyA). The lymphocyte sensitivity to cortisol was compared between these two patient groups. The cortisol IC50 values in the Tac and CyA groups were 0.09 ± 0.12 and 14.2 ± 12.7 ng/ml, respectively. Lymphocyte sensitivity to cortisol in the Tac-treated group was significantly higher than that in the CyA-treated group ( = 0.0283). On the other hand, incidences of steroid withdrawal syndrome and increases in serum creatinine concentration were not significantly different between the Tac and CyA groups. Lymphocyte sensitivity to cortisol was higher in the Tac-treated patients than that in the CyA-treated ones. Since the cortisol sensitivity of peripheral lymphocytes is suggested to be a predictive marker for safe steroid withdrawal, Tac administration shows promise in aiding successful withdrawal of steroid treatment in long-term renal transplant recipients.
淋巴细胞对内源性糖皮质激素皮质醇的敏感性可能是肾移植受者安全减少和停用类固醇的生物学标志物。我们比较了接受他克莫司(Tac)治疗的移植受者与接受环孢素治疗的移植受者外周淋巴细胞对皮质醇的敏感性。在44例已减少或停用类固醇治疗的肾移植患者中,研究了皮质醇对T细胞有丝分裂原刺激的外周淋巴细胞增殖的抑制作用。44例患者中,20例接受Tac治疗,另外24例接受环孢素A(CyA)治疗。比较了这两组患者淋巴细胞对皮质醇的敏感性。Tac组和CyA组的皮质醇IC50值分别为0.09±0.12和14.2±12.7 ng/ml。Tac治疗组淋巴细胞对皮质醇的敏感性显著高于CyA治疗组(P = 0.0283)。另一方面,Tac组和CyA组之间类固醇撤药综合征的发生率和血清肌酐浓度的升高没有显著差异。Tac治疗患者的淋巴细胞对皮质醇的敏感性高于CyA治疗患者。由于外周淋巴细胞对皮质醇的敏感性被认为是安全停用类固醇的预测标志物,因此Tac给药有望帮助长期肾移植受者成功停用类固醇治疗。