Smith C I, Hammarström L, Matell G, Nilsson B Y
Eur Neurol. 1983;22(4):272-82. doi: 10.1159/000115571.
Penicillamine and derivatives of this drug were tested for lymphocyte-activating properties. D- as well as L-penicillamine induced in vitro DNA synthesis in mouse splenocytes, whereas D-penicillamine methyl ester, N-acetyl-D-penicillamine and D-penicillamine disulfide were devoid of stimulatory properties. Lymphocytes from athymic mice were also responsive. However, we were unable to detect an increased antibody secretion in mouse spleen cell cultures exposed to penicillamine. Human peripheral blood lymphocytes from healthy individuals as well as from patients with penicillamine-induced myasthenia gravis only gave minor proliferative responses after in vitro penicillamine exposure. Furthermore, there were no differences in proliferative capacity between these two groups. Cultivated human peripheral blood or spleen cells were not activated to antibody secretion in the presence of penicillamine. There were no signs of myasthenia gravis using single-fiber electromyography recordings in patients with rheumatoid arthritis being on penicillamine treatment or in mice from several different mouse strains receiving penicillamine in their drinking water. However, NZB/NZW hybrid mice receiving penicillamine had increased amounts of antinuclear and anti-dsDNA antibodies.
对青霉胺及其衍生物的淋巴细胞激活特性进行了测试。D-青霉胺和L-青霉胺均可诱导小鼠脾细胞的体外DNA合成，而D-青霉胺甲酯、N-乙酰-D-青霉胺和二硫化D-青霉胺则不具有刺激特性。无胸腺小鼠的淋巴细胞也有反应。然而，我们未能在暴露于青霉胺的小鼠脾细胞培养物中检测到抗体分泌增加。健康个体以及患有青霉胺诱导的重症肌无力患者的人外周血淋巴细胞在体外暴露于青霉胺后仅产生轻微的增殖反应。此外，这两组之间的增殖能力没有差异。在有青霉胺存在的情况下，培养的人外周血或脾细胞不会被激活而分泌抗体。在接受青霉胺治疗的类风湿性关节炎患者或在饮用水中添加青霉胺的几种不同小鼠品系的小鼠中，使用单纤维肌电图记录未发现重症肌无力的迹象。然而，接受青霉胺的NZB/NZW杂交小鼠的抗核抗体和抗双链DNA抗体数量增加。
