Black A K, Camp R D, Mallet A I, Cunningham F M, Hofbauer M, Greaves M W
Institute of Dermatology, St. Thomas's Hospital, London, United Kingdom.
J Invest Dermatol. 1990 Jul;95(1):50-4. doi: 10.1111/1523-1747.ep12873300.
The pharmacologic and clinical effects of the 5-lipoxygenase inhibitor, lonapalene, have been determined in a double-blind, placebo-controlled, topical study in ten volunteers with psoriasis. A statistically significant clinical improvement was seen in lesions treated with 2% lonapalene ointment as compared with vehicle-treated sites. Although there was a statistically significant reduction in the levels of material similar or identical to the chemoattractant arachidonate 5-lipoxygenase product, leukotriene B4, in skin chamber fluid samples from lonapalene versus vehicle treated lesions, no significant reduction in arachidonic acid or 12-hydroxy-5,8,10,14-eicosatetraenoic acid was seen. The reduction in leukotriene B4 equivalents occurred before significant clinical improvement in lesions was seen. This and the selectivity of the pharmacologic response suggest that the therapeutic effect of topical lonapalene in psoriasis might be related to inhibition of leukotriene B4 synthesis. These results support the view that 5-lipoxygenase inhibitors may be useful in the treatment of psoriasis, and that leukotriene B4 is a relevant mediator of the pathology of this disease.
在一项针对10名银屑病志愿者的双盲、安慰剂对照的局部研究中，已确定了5-脂氧合酶抑制剂洛那帕琳的药理和临床效果。与用赋形剂治疗的部位相比，用2%洛那帕琳软膏治疗的皮损出现了具有统计学意义的临床改善。尽管与赋形剂治疗的皮损相比，来自洛那帕琳治疗皮损的皮肤腔液样本中与趋化因子花生四烯酸5-脂氧合酶产物白三烯B4相似或相同的物质水平有统计学意义的降低，但花生四烯酸或12-羟基-5,8,10,14-二十碳四烯酸水平未见显著降低。白三烯B4等效物的降低在皮损出现显著临床改善之前就已发生。这一点以及药理反应的选择性表明，局部应用洛那帕琳治疗银屑病的疗效可能与抑制白三烯B4的合成有关。这些结果支持了5-脂氧合酶抑制剂可能对银屑病治疗有用的观点，并且白三烯B4是该疾病病理过程中的相关介质。
