Dowd P M, Black A K, Woollard P W, Greaves M W
Institute of Dermatolgy, United Medical School, St. Thomas' Hospital, London, UK.
Arch Dermatol Res. 1987;279(7):427-34. doi: 10.1007/BF00412586.
The arachidonate lipoxygenase products 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraenoic acid (leukotriene B4, LTB4) are potent leucocyte chemoattractants in vitro and in vivo. Both 12-HETE and LTB4-like material are found in increased amounts in lesional skin in psoriasis. Epicutaneous administration of 12(R,S)-HETE and LTB4 in normal skin evokes neutrophil and mononuclear dermal infiltrates accompanied by collections of neutrophils in the epidermis. Similar appearances result from the application of LTB4 to uninvolved skin in psoriasis. We have now investigated the effects of single and multiple epicutaneous applications of 12(R,S)-HETE and LTB4, both alone and in combination, in normal human skin and in clinically uninvolved skin of patients with psoriasis. As in the case of LTB4, erythematous responses to 12(R,S)-HETE were similar in normal skin and in psoriasis. Similar neutrophil polymorphonuclear responses were evoked by topical application of 50 ng LTB4 and 20 micrograms 12(R,S)-HETE. Application of the combination of 12(R,S)-HETE and LTB4 evoked only a partially additive erythematous response, and no evidence of an additive neutrophilotactic response was detected histologically. Multiple applications resulted in tolerance both clinically and histologically. Cross tolerance to 12(R,S)-HETE and LTB4 occurred in the majority of subjects. These results suggest that both 12(R,S)-HETE and LTB4 may be important in the production and control of the magnitude of the inflammatory events in psoriasis.
花生四烯酸脂氧合酶产物12-羟基-5,8,10,14-二十碳四烯酸（12-HETE）和5(S),12(R)-二羟基-6,8,10,14-二十碳四烯酸（白三烯B4，LTB4）在体外和体内均为有效的白细胞趋化剂。在银屑病的皮损皮肤中，12-HETE和类LTB4物质的含量均增加。在正常皮肤表皮外用12(R,S)-HETE和LTB4可引起中性粒细胞和单核细胞真皮浸润，并伴有表皮内中性粒细胞聚集。将LTB4应用于银屑病的非皮损皮肤也会产生类似表现。我们现在研究了在正常人体皮肤和银屑病患者的临床非皮损皮肤中，单独或联合单次及多次表皮外用12(R,S)-HETE和LTB4的效果。与LTB4的情况一样，正常皮肤和银屑病皮肤对12(R,S)-HETE的红斑反应相似。局部应用50 ng LTB4和20 μg 12(R,S)-HETE可引起类似的中性粒细胞多形核反应。12(R,S)-HETE和LTB4联合应用仅引起部分相加的红斑反应，组织学检查未发现相加的中性粒细胞趋化反应证据。多次应用在临床和组织学上均导致耐受性。大多数受试者对12(R,S)-HETE和LTB4产生交叉耐受性。这些结果表明，12(R,S)-HETE和LTB4在银屑病炎症事件的发生和炎症程度的控制中可能都很重要。
