硫唑嘌呤可抑制莱施-奈恩综合征患者的混合淋巴细胞反应。
Azathioprine suppresses the mixed lymphocyte reaction of patients with Lesch-Nyhan syndrome.
作者信息
Szawlowski P W, Al-Safi S A, Dooley T, Maddocks J L
出版信息
Br J Clin Pharmacol. 1985 Nov;20(5):489-91. doi: 10.1111/j.1365-2125.1985.tb05104.x.
The mixed lymphocyte reaction of Lesch-Nyhan patients (HGPRT deficient) was used to study the immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP). Mitogen stimulated lymphocytes of these patients are highly resistant to azathioprine and 6-MP. When both stimulator and responder lymphocytes in the MLR were HGPRT deficient, azathioprine (36 microM) was much more inhibitory than 6-MP (100 microM). Azathioprine produced inhibition of 98.2% and 78.5% compared with the values of 63.9% and 30.6% for 6-MP. The difference in inhibitory activity between azathioprine and 6-MP was reduced when normal stimulator lymphocytes were cultured with HGPRT deficient responder lymphocytes in the MLR. These results provide very strong evidence that the nucleotide metabolites of azathioprine and 6-MP are unnecessary for immunosuppression. They also suggest that azathioprine and 6-MP interfere with antigenic triggering of the MLR.
采用莱施-奈恩病患者（次黄嘌呤-鸟嘌呤磷酸核糖转移酶缺乏）的混合淋巴细胞反应来研究硫唑嘌呤和6-巯基嘌呤（6-MP）的免疫抑制作用。这些患者的丝裂原刺激淋巴细胞对硫唑嘌呤和6-MP具有高度抗性。当混合淋巴细胞反应中的刺激细胞和反应细胞均缺乏次黄嘌呤-鸟嘌呤磷酸核糖转移酶时，硫唑嘌呤（36微摩尔）的抑制作用比6-MP（100微摩尔）更强。硫唑嘌呤产生的抑制率分别为98.2%和78.5%，而6-MP的抑制率分别为63.9%和30.6%。当在混合淋巴细胞反应中用正常刺激淋巴细胞与缺乏次黄嘌呤-鸟嘌呤磷酸核糖转移酶的反应淋巴细胞共同培养时，硫唑嘌呤和6-MP之间的抑制活性差异减小。这些结果提供了非常有力的证据，表明硫唑嘌呤和6-MP的核苷酸代谢产物对于免疫抑制并非必需。它们还表明硫唑嘌呤和6-MP干扰了混合淋巴细胞反应的抗原触发。
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