Harris R R, Mackin W M, Batt D G, Rakich S M, Collins R J, Bruin E M, Ackerman N R
Medical Products Department, E.I. du Pont de Nemours and Company, Wilmington, Del.
Skin Pharmacol. 1990;3(1):29-40. doi: 10.1159/000210838.
The possible utility of DuP 654, a potent 5-lipoxygenase inhibitor, for treating human inflammatory skin disease was investigated in murine skin treated with 1.0 mg arachidonic acid (AA). When DuP 654 was applied to murine skin treated with AA, it inhibited the resulting inflammation and influx of cells. High performance liquid chromatography and radioimmunoassay analysis of lipid extracts from AA-treated ears indicated that the influx of polymorphonuclear leukocytes (PMN) was temporally preceded by an appearance of significant amounts of 5-HETE (6.7 +/- 1.4 ng/ear) and Leukotriene B4 LTB4 0.92 +/- 0.2 ng/ear) when compared with extracts of untreated ears (5-HETE, 02 +/- 0.3 ng/ear; LTB4, less than 0.1 ng/ear). The levels of the 5-lipoxygenase products were reduced by treatment with 10 micrograms/ear DUP 654. Lipid extracts from AA-treated ears contain chemotactic activity for human PMN and this chemotactic activity in the AA-treated ears could be reduced but not eliminated by immunosorption with anti-LTB4 antibodies coupled to protein A-agarose. The appearance of the chemotactic activity was inhibited by DuP 654. Taken together, these data suggest that DuP 654 may have utility in human inflammatory skin disease.
在以1.0毫克花生四烯酸（AA）处理的小鼠皮肤中，研究了强效5-脂氧合酶抑制剂DuP 654用于治疗人类炎性皮肤病的潜在效用。当将DuP 654应用于经AA处理的小鼠皮肤时，它抑制了由此产生的炎症和细胞流入。对经AA处理的耳部脂质提取物进行的高效液相色谱和放射免疫分析表明，与未处理耳部的提取物（5-HETE，0.2±0.3纳克/耳；白三烯B4，小于0.1纳克/耳）相比，多形核白细胞（PMN）的流入在时间上先于大量5-HETE（6.7±1.4纳克/耳）和白三烯B4（LTB4，0.92±0.2纳克/耳）的出现。用10微克/耳的DUP 654处理可降低5-脂氧合酶产物的水平。经AA处理的耳部脂质提取物对人PMN具有趋化活性，并且经AA处理的耳部中的这种趋化活性可通过与偶联至蛋白A-琼脂糖的抗LTB4抗体进行免疫吸附而降低但不能消除。趋化活性的出现受到DuP 654的抑制。综上所述，这些数据表明DuP 654可能对人类炎性皮肤病有用。
