Bacon P A, Salmon M
Department of Rheumatology, University of Birmingham, U.K.
Scand J Rheumatol Suppl. 1987;64:17-24. doi: 10.3109/03009748709096717.
The slow acting anti-rheumatic drugs (SARDS) are a chemically heterogeneous group. They produce a more profound effect on clinical and biochemical aspects of rheumatoid arthritis than do the aspirin-like non steroidals. The similarities in their clinical effects suggest that they have a common mode of action. Review of the known activity of SARDs on different cell types at various anatomical sites suggest that in fact different SARD drugs act in differing and sometimes conflicting ways. The site of action of SARDs within the body--whether at the level of synovial inflammation or of the systemic immune response--is largely undetermined. The effects produced by a single agent in vivo and in vitro are not always the same so a single mode of action, for example through possession of a thiol group, cannot explain the effects of all SARDs. Indeed a single agent such as aurothiomalate may show multiple effects and the same is now shown to be true for the newer agent sulphasalazine. A unifying hypothesis is put forward to explain the clinical similarities but different cellular effects. It is proposed that all SARDs act on some aspect of the central reaction in the ongoing immune response where antigen presentation to T helper cells results in interleukin 2 production and the generation of activated T cells. The precise site affected in this cell to cell/monokine reaction will vary between drugs, but the overall effect of blocking this will be similar for all drugs, both in short term clinical benefit and in the problem of disease flares after withdrawal of therapy.
慢作用抗风湿药（SARDS）是一类化学性质各异的药物。与阿司匹林样非甾体类药物相比，它们对类风湿性关节炎的临床和生化方面产生更深远的影响。它们临床效果的相似性表明它们有共同的作用方式。回顾已知的SARDs在不同解剖部位对不同细胞类型的作用表明，实际上不同的SARD药物作用方式不同，有时甚至相互矛盾。SARDs在体内的作用部位——无论是在滑膜炎症水平还是全身免疫反应水平——在很大程度上尚未确定。单一药物在体内和体外产生的效果并不总是相同的，因此单一的作用方式，例如通过拥有一个巯基，无法解释所有SARDs的效果。事实上，单一药物如金硫代苹果酸可能会显示出多种效果，现在已证明新型药物柳氮磺胺吡啶也是如此。提出了一个统一的假说来解释临床相似性但细胞效应不同的现象。有人提出，所有SARDs都作用于正在进行的免疫反应中的中心反应的某个方面，在这个反应中，抗原呈递给辅助性T细胞会导致白细胞介素2的产生和活化T细胞的生成。不同药物在这种细胞间/单核因子反应中影响的具体部位会有所不同，但阻断这一反应的总体效果对所有药物来说都是相似的，无论是在短期临床益处还是在停药后疾病复发的问题上。
