Versluis D J, Bijma A M, Vaessen L M, Weimar W
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Int J Immunopharmacol. 1989;11(2):157-64. doi: 10.1016/0192-0561(89)90067-2.
Long term CsA therapy did not interfere with the basal levels of natural killer (NK) activity in stable cadaveric renal transplant recipients. However, 3 months after changing immunosuppressive therapy from CsA to AZA, NK activity was significantly decreased (36 +/- 25% vs 19 +/- 15%, P less than 0.01). Following in vitro exposure to IFN-gamma an increase in NK activity from 36 to 44% (P less than 0.05) could be induced during CsA therapy but this was no longer observed after conversion to AZA (19 to 22%, N.S.). A prominent decline in the number of NK cells expressing the surface receptor for the Fc portion of IgG was also found postconversion. The IFN-gamma production capacity after mitogen stimulation of unprimed lymphocytes was more depressed during CsA than during AZA therapy (median 25 vs 80 U/ml 10(6) cells, P less than 0.05), suggesting a reversible inhibition of CsA on lymphokine production. Despite the better IFN-gamma production capacity, both the activity, inducibility and number of NK cells were significantly lower under AZA therapy than under CsA therapy. These findings indicate that CsA exerts its immunosuppressive action without an important interference with NK activity. Monitoring mononuclear cells showed a decrease in absolute numbers of all phenotypically distinct cells studied after conversion. The prominent decrease in CD 8 cells resulted in an increase of CD 4/CD 8 ratio.
长期使用环孢素A（CsA）治疗并未干扰稳定的尸体肾移植受者的自然杀伤（NK）细胞活性基础水平。然而，将免疫抑制治疗从CsA转换为硫唑嘌呤（AZA）3个月后，NK细胞活性显著降低（36±25%对19±15%，P<0.01）。在CsA治疗期间，体外暴露于γ干扰素（IFN-γ）后，NK细胞活性可从36%增加至44%（P<0.05），但转换为AZA后不再观察到这种增加（19%至22%，无统计学意义）。转换治疗后还发现，表达IgG Fc段表面受体的NK细胞数量显著下降。与AZA治疗相比，CsA治疗期间丝裂原刺激未致敏淋巴细胞后的IFN-γ产生能力受到更明显的抑制（中位数分别为25 U/ml对80 U/ml 10⁶个细胞，P<0.05），提示CsA对淋巴因子产生有可逆性抑制作用。尽管IFN-γ产生能力较好，但AZA治疗下NK细胞的活性、诱导性和数量均显著低于CsA治疗。这些发现表明，CsA在发挥免疫抑制作用时对NK细胞活性无重要干扰。监测单核细胞发现，转换治疗后所研究的所有表型不同细胞的绝对数量均减少。CD 8细胞显著减少导致CD 4/CD 8比值增加。
