Lee J C, Votta B, Griswold D E, Hanna N
Department of Immunology, Smith Kline & French Laboratories, Swedeland, PA 19479.
Agents Actions. 1989 Jun;27(3-4):280-1. doi: 10.1007/BF01972797.
The effects of several anti-inflammatory and anti-arthritic drugs on the in vitro production of interleukin-1 by human monocytes were examined. SK&F 86002-A2 was shown to be a potent inhibitor of IL-1 production with a 50% inhibitory concentration (IC50) of 1.3 +/- 0.5 microM. Standard compounds which inhibit the cyclooxygenase (CO) or CO and 5-lipoxygenase (5LO) pathways of arachidonic acid metabolism did not inhibit IL-1 production at nontoxic concentrations. Analysis of SK&F 86002 analogs also showed no clear correlation between 5LO and IL-1 synthesis inhibitory activity. The precise mechanism of action is not known except that it is post-transcriptional. Thus, SK&F 86002 may serve as a useful reagent in the understanding of the synthetic, processing and/or secretory pathways of interleukin-1, and may provide important insight into the treatment of disease states where aberrant IL-1 production is implicated.
研究了几种抗炎和抗关节炎药物对人单核细胞体外产生白细胞介素-1的影响。结果表明，SK&F 86002-A2是白细胞介素-1产生的有效抑制剂，其50%抑制浓度（IC50）为1.3±0.5微摩尔。抑制花生四烯酸代谢的环氧化酶（CO）或CO和5-脂氧合酶（5LO）途径的标准化合物在无毒浓度下不抑制白细胞介素-1的产生。对SK&F 86002类似物的分析也表明，5LO与白细胞介素-1合成抑制活性之间没有明显的相关性。除了其作用是转录后水平外，其确切作用机制尚不清楚。因此，SK&F 86002可能是一种有用的试剂，有助于了解白细胞介素-1的合成、加工和/或分泌途径，并可能为治疗与白细胞介素-1异常产生有关的疾病状态提供重要的见解。
