Danis V A, Franic G M, Rathjen D A, Laurent R M, Brooks P M
Kolling Institute, Royal North Shore Hospital, Sydney, Australia.
Ann Rheum Dis. 1992 Aug;51(8):946-50. doi: 10.1136/ard.51.8.946.
Interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF) alpha are pleiotropic cytokines produced predominantly by macrophages which have been implicated in the pathogenesis of rheumatoid arthritis (RA). Sulphasalazine has been shown to have disease modifying properties and to inhibit the production of cytokines in vitro. To evaluate the effect of sulphasalazine on cytokine production in vivo, serum cytokine levels were measured in a group of patients with RA entered into a randomised controlled trial. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF alpha were measured at baseline and at two monthly intervals for six months in 17 patients receiving sulphasalazine and in 22 patients treated with placebo. The two groups of patients had a similar age and sex distribution, had had RA for less than a year, had no joint erosions, and had not been treated previously with any other disease modifying drugs. In the 39 patients studied IL-1 alpha was detected (> 0.1 ng/ml) at baseline in 14 patients (median 0.24 ng/ml), IL-1 beta in 25 patients (median 1.0 ng/ml), TNF alpha in 27 patients (median 1.2 ng/ml), and IL-6 in 33 patients (median 0.44 ng/ml). In the group treated with sulphasalazine there was a progressive and significant decline in serum IL-1 alpha, IL-1 beta, and TNF alpha levels over the six month period (median levels at six months were < 0.1, 0.12, and 0.44 ng/ml respectively). Interleukin 6 levels were significantly reduced only at the four month time point (median level of 0.23 ng/ml). These reductions were associated with improvements in clinical and laboratory measures of disease activity. In contrast patients receiving the placebo showed no changes in serum cytokine levels and no improvement in clinical and laboratory indices of disease activity. These results suggest that sulphasalazine may exert its disease modifying effect partly by suppressing cytokine production in vivo.
白细胞介素1（IL-1）、IL-6和肿瘤坏死因子（TNF）α是主要由巨噬细胞产生的多效性细胞因子，它们与类风湿关节炎（RA）的发病机制有关。柳氮磺胺吡啶已被证明具有改善病情的特性，并能在体外抑制细胞因子的产生。为了评估柳氮磺胺吡啶在体内对细胞因子产生的影响，在一组进入随机对照试验的RA患者中测量了血清细胞因子水平。在17名接受柳氮磺胺吡啶治疗的患者和22名接受安慰剂治疗的患者中，在基线时以及每隔两个月测量一次血清IL-1α、IL-1β、IL-6和TNFα水平，持续六个月。两组患者的年龄和性别分布相似，患RA不到一年，无关节侵蚀，且此前未接受过任何其他改善病情的药物治疗。在研究的39名患者中，14名患者（中位数为0.24 ng/ml）在基线时检测到IL-1α（>0.1 ng/ml），25名患者（中位数为1.0 ng/ml）检测到IL-1β，27名患者（中位数为1.2 ng/ml）检测到TNFα，33名患者（中位数为0.44 ng/ml）检测到IL-6。在接受柳氮磺胺吡啶治疗的组中，在六个月期间血清IL-1α、IL-1β和TNFα水平呈逐渐且显著下降（六个月时的中位数水平分别<0.1 ng/ml、0.12 ng/ml和0.44 ng/ml）。白细胞介素6水平仅在四个月时间点显著降低（中位数水平为0.23 ng/ml）。这些降低与疾病活动的临床和实验室指标的改善相关。相比之下，接受安慰剂的患者血清细胞因子水平没有变化，疾病活动的临床和实验室指标也没有改善。这些结果表明，柳氮磺胺吡啶可能部分通过抑制体内细胞因子的产生来发挥其改善病情的作用。
