Dong M K, Wilburn D J, Conroy M C, Gilbertsen R B
Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105.
Agents Actions. 1991 Sep;34(1-2):53-5. doi: 10.1007/BF01993236.
CI-959 (5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-yl-benzo [b]-thiophene-2-carboxamide), an antiallergy compound, blocked release of IL-2 from Con A stimulated rat splenocytes and human lymphocytes with respective IC50s of 19.1 and 23.1 microM. Inhibition of IL-2 production required the presence of CI-959 in culture medium for the first 9 hr. CI-959 also inhibited Con A-stimulated rat and human lymphocyte proliferation with IC50s of 4.7 and 5.4 microM, respectively. Inhibition of the Con A proliferative response could not be overcome by exogenous recombinant human IL-2 (300 units/ml) in either the rat or human systems. Although potent in the human mixed lymphocyte reaction (IC50 = 3.5 microM), CI-959 was less effective in blocking the PHA response (IC50 = 43.9 microM), and had minimal effect on the release of IL-1 and TNF alpha from LPS-stimulated human monocytes. These findings suggest that CI-959 selectively inhibits some lymphocyte functions, as opposed to monocyte functions, and that among these is the production of IL-2.
CI-959（5-甲氧基-3-（1-甲乙氧基）-N-1H-四唑-5-基-苯并[b]噻吩-2-甲酰胺）是一种抗过敏化合物，它能抑制刀豆蛋白A刺激的大鼠脾细胞和人淋巴细胞释放白细胞介素-2，其半数抑制浓度（IC50）分别为19.1和23.1微摩尔。抑制白细胞介素-2的产生需要在培养的最初9小时培养基中存在CI-959。CI-959还能抑制刀豆蛋白A刺激的大鼠和人淋巴细胞增殖，其IC50分别为4.7和5.4微摩尔。在大鼠或人系统中，外源性重组人白细胞介素-2（300单位/毫升）都无法克服CI-959对刀豆蛋白A增殖反应的抑制作用。尽管CI-959在人混合淋巴细胞反应中作用显著（IC50 = 3.5微摩尔），但它在阻断植物血凝素反应方面效果较差（IC50 = 43.9微摩尔），并且对脂多糖刺激的人单核细胞释放白细胞介素-1和肿瘤坏死因子α的影响极小。这些发现表明，CI-959选择性地抑制某些淋巴细胞功能，而非单核细胞功能，其中包括白细胞介素-2的产生。
