Kobashi H, Adachi T, Tsubota T, Asano K, Fukai M, Namba J, Izumi K, Hoshijima T, Miura H, Sezaki T
Rinsho Ketsueki. 1989 Mar;30(3):282-8.
The in vitro effects of the causative drugs and lymphocytes from the patients with agranulocytosis were tested against granulocyte-macrophage colony formation (CFU-C) of bone marrow cells from normal individuals and the patients in recovery stage. A semisolid culture system was used for CFU-C assay. The drug concentrations were adjusted to the therapeutic levels in sera, and the lymphocytes were obtained from the patient's peripheral blood. Three patients with agranulocytosis and one patient with pancytopenia caused by disopyramide, methimazole, sodium valproate, and Towasaal, respectively, were examined. Each of the four drugs except disopyramide suppressed the CFU-C of normal and patient's bone marrow cells in a dose-dependent manner. When the patient's bone marrow cells were cultured with respective drugs and their own lymphocytes or with the culture supernatant of the drug and lymphocytes, CFU-C suppressions was significantly augmented. Phenacetin, an agent of Towasaal, significantly suppressed CFU-C and also CFU-E. These results indicate that humoral factor(s) produced from patient's lymphocytes by reacting with the drugs may function as an immunological mechanism in the patients with drug-induced agranulocytosis.
对粒细胞缺乏症患者的致病药物和淋巴细胞的体外作用，针对正常个体及恢复期患者骨髓细胞的粒细胞 - 巨噬细胞集落形成（CFU - C）进行了检测。采用半固体培养系统进行CFU - C检测。将药物浓度调整至血清中的治疗水平，并从患者外周血中获取淋巴细胞。分别检测了由丙吡胺、甲巯咪唑、丙戊酸钠和托瓦沙尔（Towasaal）导致粒细胞缺乏症的3例患者以及导致全血细胞减少症的1例患者。除丙吡胺外，其余四种药物均以剂量依赖方式抑制正常及患者骨髓细胞的CFU - C。当患者骨髓细胞与各自药物及其自身淋巴细胞共同培养，或与药物和淋巴细胞的培养上清液共同培养时，CFU - C抑制作用显著增强。托瓦沙尔的成分非那西丁显著抑制CFU - C以及CFU - E。这些结果表明，患者淋巴细胞与药物反应产生的体液因子可能在药物性粒细胞缺乏症患者中作为一种免疫机制发挥作用。
