普伐他汀对体内自然杀伤细胞活性及体外细胞毒性T淋巴细胞活性的抑制作用。

The inhibitory effects of pravastatin on natural killer cell activity in vivo and on cytotoxic T lymphocyte activity in vitro.

作者信息

Katznelson S, Wang X M, Chia D, Ozawa M, Zhong H P, Hirata M, Terasaki P I, Kobashigawa J A

机构信息

Division of Nephrology, University of California, Davis, School of Medicine, Sacramento, USA.

出版信息

J Heart Lung Transplant. 1998 Apr;17(4):335-40.

PMID:9588577

Abstract

BACKGROUND

We have reported that heart transplant recipients treated with pravastatin demonstrate decreases in the incidence of clinically severe acute rejection episodes, the incidence and progression of transplant coronary vasculopathy, and natural killer cytotoxicity. These patients also exhibited a significant improvement in 1-year allograft survival. Because of these clinical findings suggesting an immunosuppressive effect of pravastatin unique to transplant recipients and the unclear role of natural killer cells in allograft rejection, we postulated that pravastatin may exert its immunomodulatory effect by acting with cyclosporine to alter T lymphocyte function.

METHODS

Twenty patients randomized into an ongoing trial of pravastatin after heart transplantation were monitored serially for natural killer cell cytotoxicity. In a separate experiment, lymphocytes isolated from normal volunteers were treated with various combinations of pravastatin and cyclosporine and tested for cytotoxic T lymphocyte toxicity in a one-way mixed lymphocyte reaction.

RESULTS

Pravastatin-treated heart transplant recipients exhibited a decrease in natural killer cell cytotoxicity (9.8% mean natural killer cell cytotoxicity vs 22.1% in the control group, p < 0.01). In the one-way mixed lymphocyte reaction with blood obtained from control subjects, there was a synergistic inhibition of cytotoxic T lymphocyte activity when the cells were cultured in a combination of pravastatin and cyclosporine (20.3% mean cytotoxicity of target cells vs 41.4% in the control group, p < 0.01).

CONCLUSIONS

Pravastatin exerts an immunosuppressive effect in heart transplant recipients as expressed by a reduction in rejection and natural killer cell cytotoxicity. Pravastatin and cyclosporine act synergistically to reduce cytotoxic T lymphocyte activity. This synergistic effect of pravastatin and cyclosporine may explain why this immunosuppressive effect is unique to transplant recipients.

摘要

背景

我们曾报道，接受普伐他汀治疗的心脏移植受者临床严重急性排斥反应的发生率、移植冠状动脉血管病变的发生率及进展以及自然杀伤细胞细胞毒性均有所降低。这些患者的1年移植物存活率也有显著提高。鉴于这些临床发现提示普伐他汀对移植受者具有独特的免疫抑制作用，且自然杀伤细胞在移植物排斥中的作用尚不清楚，我们推测普伐他汀可能通过与环孢素共同作用来改变T淋巴细胞功能，从而发挥其免疫调节作用。

方法

对20名随机纳入心脏移植后普伐他汀正在进行试验的患者进行连续监测，检测其自然杀伤细胞毒性。在另一项实验中，用普伐他汀和环孢素的不同组合处理从正常志愿者分离的淋巴细胞，并在单向混合淋巴细胞反应中检测其细胞毒性T淋巴细胞毒性。

结果

接受普伐他汀治疗的心脏移植受者自然杀伤细胞毒性降低（平均自然杀伤细胞毒性为9.8%，而对照组为22.1%，p<0.01）。在与对照组受试者血液进行的单向混合淋巴细胞反应中，当细胞在普伐他汀和环孢素组合中培养时，细胞毒性T淋巴细胞活性受到协同抑制（靶细胞平均细胞毒性为20.3%，而对照组为41.4%，p<0.01）。