Lee J C, Griswold D E, Votta B, Hanna N
Department of Immunology, Smith Kline and French Laboratories, Philadelphia, PA 19101.
Int J Immunopharmacol. 1988;10(7):835-43. doi: 10.1016/0192-0561(88)90007-0.
The effects of several anti-inflammatory/anti-arthritic drugs on the in vitro production of interleukin-1 (IL-1) by human monocytes were examined. SK&F 86002, a novel dihydroimidazo thiazoline which inhibits both 5-lipoxygenase- and cyclooxygenase-mediated arachidonate metabolism was shown to be a potent inhibitor of IL-1 production by LPS-stimulated human monocytes. The inhibition was dose-dependent (IC50 = 1.30 +/- 1 microM), reversible and was independent of the concentration or type of stimulus used. The compound also inhibited cell-associated IL-1 activity. The compound did not exert general inhibitory effects on such parameters as adherence, cytotoxic function and protein synthesis of the monocytes. Other cyclooxygenase and/or 5-lipoxygenase inhibitors of arachidonic acid metabolism tested, with the exception of nordihydroguaiaretic acid, were inactive in inhibiting monocyte IL-1 production suggesting that the inhibition of IL-1 production by 86002 may be dissociated from its inhibition of the fatty acid oxygenases. The inhibition of IL-1 production by SK&F 86002 adds another facet of drug action contributing to its spectrum of anti-inflammatory activities.
研究了几种抗炎/抗关节炎药物对人单核细胞体外产生白细胞介素-1（IL-1）的影响。SK&F 86002是一种新型二氢咪唑并噻唑啉，它能抑制5-脂氧合酶和环氧化酶介导的花生四烯酸代谢，已证明它是脂多糖刺激的人单核细胞产生IL-1的有效抑制剂。这种抑制作用呈剂量依赖性（IC50 = 1.30 +/- 1 microM），具有可逆性，且与所用刺激物的浓度或类型无关。该化合物还抑制细胞相关的IL-1活性。该化合物对单核细胞的黏附、细胞毒性功能和蛋白质合成等参数没有普遍的抑制作用。除去甲二氢愈创木酸外，所测试的其他花生四烯酸代谢的环氧化酶和/或5-脂氧合酶抑制剂对单核细胞IL-1的产生均无活性，这表明86002对IL-1产生的抑制作用可能与其对脂肪酸加氧酶的抑制作用无关。SK&F 86002对IL-1产生的抑制作用为其抗炎活性谱增添了另一个药物作用方面。
