Finkelstein A E, Roisman F R, Walz D T
Inflammation. 1977 Jun;2(2):143-50. doi: 10.1007/BF00918676.
Auranofin, an oral chrysotherapeutic agent effective in the treatment of rheumatoid arthritis (RA), was found to be a potent, noncytotoxic inhibitor of IgG-RF immune complex-induced lysosomal enzyme release (LER) from human leukocytes. At a concentration of 1 microg Au/ml (5 microM), auranofin produced a marked reduction in beta-glucuronidase (100%), acid phosphatase (88%), and lysozyme (72%) release. In contrast, gold sodium thiosulfate (GST, an injectable gold compound) had no inhibitory activity on LER at equivalent gold concentrations (i.e., 1 microg Au/ml) and only modest activity (less than 36% inhibition) at concentrations as high as 40 microg Au/ml. The 50% inhibitory dose (LD50) of auranofin on LER was calculated to be 3-4 microM (0.6-0.8 microg Au/ml). Blood gold levels in auranofin-treated RA patients were found to be within the range required for in vitro inhibition of LER, and correlated with decreases in IgG, RF titers, and IgG-RF immune-complex formation in vitro. These results suggest that the therapeutic action of auranofin may be caused, at least in part, by inhibition of LER and/or decreases in immune-complex formation.
金诺芬是一种治疗类风湿性关节炎（RA）有效的口服金制剂，它是一种有效的、无细胞毒性的抑制剂，可抑制IgG-RF免疫复合物诱导的人白细胞溶酶体酶释放（LER）。在浓度为1微克金/毫升（5微摩尔）时，金诺芬可使β-葡萄糖醛酸酶释放（100%）、酸性磷酸酶释放（88%）和溶菌酶释放（72%）显著减少。相比之下，硫代硫酸钠金（GST，一种可注射的金化合物）在等效金浓度（即1微克金/毫升）时对LER无抑制活性，在高达40微克金/毫升的浓度时仅有适度活性（抑制率小于36%）。金诺芬对LER的50%抑制剂量（LD50）经计算为3 - 4微摩尔（0.6 - 0.8微克金/毫升）。在接受金诺芬治疗的RA患者中，发现血金水平处于体外抑制LER所需的范围内，并且与体外IgG、RF滴度以及IgG-RF免疫复合物形成的减少相关。这些结果表明，金诺芬的治疗作用可能至少部分是由抑制LER和/或免疫复合物形成减少所引起的。
