Fogh K, Søgaard H, Herlin T, Kragballe K
Department of Dermatology, Marselisborg Hospital, Aarhus C, Denmark.
J Am Acad Dermatol. 1988 Feb;18(2 Pt 1):279-85. doi: 10.1016/s0190-9622(88)70040-7.
Psoriatic skin lesions are characterized by elevated levels of 5- and 12-lipoxygenase products (leukotrienes B4, C4, and D4, and 12-hydroxyeicosatetraenoic acid [12-HETE]), which can stimulate epidermal proliferation and induce skin inflammation. 15-Hydroxyeicosatetraenoic acid (15-HETE) has the potential to inhibit the activity of 5- and 12-lipoxygenases. The purpose of the present study was to determine the therapeutic effect of intralesional injections of 15-HETE. 15-HETE was formed by oxidation of arachidonic acid by soybean lipoxygenase, purified by reversed-phase high-performance liquid chromatography, and identified by mass spectrometric analysis. Thirteen patients took part in the investigation. Plaques with a diameter of approximately 1 cm were injected with 0.1 ml of 10 mumol/L 15-HETE, 0.1 ml of 1 mumol/L 15-HETE, or 0.1 ml of saline weekly. After 3 weeks the effect was evaluated clinically and histologically by an observer uniformed of the treatment given. We found that plaques injected with 10 mumol/L 15-HETE had cleared completely in four patients and improved considerably in seven. In one patient minimal improvement only was seen and in one patient no change was observed. Injection of 1 mumol/L 15-HETE was without effect in 11 patients and improvement was observed in two patients. Of the plaques injected with saline, minimal improvement was observed in one patient; otherwise the plaques had not changed. Injection of 0.1 ml of 10 mumol/L 15-HEPE (identical to 15-HETE except for five double bonds instead of four) induced only minimal improvement in one of four patients. The results imply that 15-HETE by a dose-dependent and stereospecific mechanism can improve psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
银屑病皮肤损害的特征是5-脂氧合酶和12-脂氧合酶产物(白三烯B4、C4和D4,以及12-羟基二十碳四烯酸[12-HETE])水平升高,这些产物可刺激表皮增殖并诱发皮肤炎症。15-羟基二十碳四烯酸(15-HETE)有可能抑制5-脂氧合酶和12-脂氧合酶的活性。本研究的目的是确定皮损内注射15-HETE的治疗效果。15-HETE由大豆脂氧合酶氧化花生四烯酸形成,通过反相高效液相色谱法纯化,并通过质谱分析进行鉴定。13名患者参与了该研究。直径约1 cm的斑块每周注射0.1 ml 10 μmol/L 15-HETE、0.1 ml 1 μmol/L 15-HETE或0.1 ml生理盐水。3周后,由对所给予治疗不知情的观察者进行临床和组织学评估。我们发现,注射10 μmol/L 15-HETE的斑块在4名患者中完全清除,7名患者有显著改善。1名患者仅有轻微改善,1名患者无变化。注射1 μmol/L 15-HETE对11名患者无效,2名患者有改善。在注射生理盐水的斑块中,1名患者有轻微改善;否则斑块没有变化。注射0.1 ml 10 μmol/L 15-HEPE(除有五个双键而非四个双键外与15-HETE相同)在4名患者中的1名中仅引起轻微改善。结果表明,15-HETE可通过剂量依赖性和立体特异性机制改善银屑病。(摘要截短为250字)