Gifford R R, Tilberg A F
Department of Surgery, Pennsylvania State College of Medicine, Hershey 17033.
J Surg Res. 1988 Sep;45(3):276-80. doi: 10.1016/0022-4804(88)90075-3.
Cimetidine has been shown to up-regulate proliferative and cytotoxic immune responses, which are mediated in part by an increase in interleukin-2 (IL-2) production. Cyclosporine achieves its immunosuppressive effect mainly through inhibition of IL-2 production. A recent clinical report of renal allograft recipients with elevated serum creatinine levels while on a histamine type-2 receptor antagonist raised concern whether the cimetidine increase in IL-2 production was counterbalancing the cyclosporine inhibition of IL-2 and thereby increasing alloreactivity to the transplant. We therefore measured IL-2 production of mitogen-stimulated murine spleen cells with or without cimetidine and cyclosporine and in combination of these two drugs. Cimetidine (10(-4) and 10(-5) M) completely reversed the cyclosporine (0.1 ng/ml and 1 ng/ml)-induced 25 and 41% inhibitions of IL-2, respectively. Cyclosporine (10 ng/ml) reduced IL-2 by 64% and cimetidine partially reversed this inhibition to 48%. All cimetidine groups which reduced the cyclosporine effect on IL-2 were statistically significant (P less than 0.05). These data raise concern about the safety of giving histamine type-2 receptor antagonists to allograft recipients without increasing alloreactivity due to a relative increase in IL-2.
西咪替丁已被证明可上调增殖性和细胞毒性免疫反应，这部分是由白细胞介素-2（IL-2）产生增加介导的。环孢素主要通过抑制IL-2的产生来实现其免疫抑制作用。最近有一份关于肾移植受者的临床报告，这些受者在服用组胺2型受体拮抗剂时血清肌酐水平升高，这引发了人们的担忧，即西咪替丁增加IL-2的产生是否抵消了环孢素对IL-2的抑制作用，从而增加了对移植的同种异体反应性。因此，我们测量了有或没有西咪替丁和环孢素以及这两种药物联合使用时丝裂原刺激的小鼠脾细胞的IL-2产生。西咪替丁（10^(-4)和10^(-5) M）分别完全逆转了环孢素（0.1 ng/ml和1 ng/ml）诱导的对IL-2的25%和41%的抑制作用。环孢素（10 ng/ml）使IL-2减少了64%，而西咪替丁部分逆转了这种抑制作用，使其降至48%。所有降低环孢素对IL-2作用的西咪替丁组均具有统计学意义（P小于0.05）。这些数据引发了人们对给移植受者使用组胺2型受体拮抗剂的安全性的担忧，因为IL-2相对增加可能会增加同种异体反应性。
