Gifford R R, Hatfield S M, Schmidtke J R
Transplantation. 1980 Feb;29(2):143-8. doi: 10.1097/00007890-198002000-00011.
The effect of Cimetidine, a histamine-type 2 receptor antagonist, was evaluated on the in vitro proliferative response of normal human peripheral blood lymphocytes (PBLs). Cimetidine (10(-3) to 10(-8) M) increased mitogen-induced blastogenesis by 22% (phytohemagglutinin (PHA) and by 27% (pokeweed) over nondrug-treated control values (P less than 005 for PHA and pokeweed). Preincubation of PBLs with Cimetidine further augmented blastogenesis as much as 2- to 3-fold (P less than 0.005 for both mitogens). Multiple testing of the same normal subject demonstrated consistent reproducibility of increased proliferation by Cimetidine. Similar statistically significant amplifications of the proliferative res-ponse were observed when bacterial antigen (streptokinase-streptodornase) or alloantigen was used to induce blastogenesis. Optimally effective concentrations of Cimetidine ranged from 10(-5) to 10(-7) M, which corresponds to expected clinical serum levels. These observations suggest that a histamine-type 2 receptor antagonist is capable of modulating the proliferative response of PBLs in the absence of exogenously added histamine. The immunoregulatory implication of this Cimetidine-induced proliferative augmentation is discussed in relation to clinical transplantation and cancer immunotherapy.
对组胺2型受体拮抗剂西咪替丁在体外对正常人外周血淋巴细胞（PBLs）增殖反应的作用进行了评估。西咪替丁（10⁻³至10⁻⁸M）使丝裂原诱导的母细胞生成增加，与未用药物处理的对照值相比，植物血凝素（PHA）诱导的增加了22%，商陆诱导的增加了27%（PHA和商陆的P均小于0.005）。PBLs与西咪替丁预孵育进一步使母细胞生成增加2至3倍（两种丝裂原的P均小于0.005）。对同一正常受试者的多次检测表明，西咪替丁使增殖增加具有一致的可重复性。当使用细菌抗原（链激酶-链道酶）或同种异体抗原诱导母细胞生成时，观察到增殖反应有类似的统计学显著增强。西咪替丁的最佳有效浓度范围为10⁻⁵至10⁻⁷M，这与预期的临床血清水平相对应。这些观察结果表明，组胺2型受体拮抗剂能够在没有外源性添加组胺的情况下调节PBLs的增殖反应。本文讨论了西咪替丁诱导的增殖增强在临床移植和癌症免疫治疗方面的免疫调节意义。
