白三烯B4、5-羟色胺和白介素-1β在玫瑰糠疹中的表达及意义
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摘要
目的:玫瑰糠疹(Pityriasia rosea, PR)是一种临床较为常见的炎症性皮肤病,皮损为大小不等的圆形或椭圆形的玫瑰色斑疹,其表面附有糠状鳞屑,多发生在躯干及四肢近端。病因及发病机制尚不清楚,涉及病毒感染、变态反应、自身免疫、遗传性过敏症等多种学说。白三烯B4(leukotriene B4, LTB4)在变态反应、炎症、和免疫系统中发挥着重要作用。LTB4是肥大细胞、嗜碱性粒细胞激活后立即合成的介质,通过脱颗粒而向细胞外释放,作用于其它细胞和组织而参与变态反应,在I型变态反应速发期,可以与白介素-4 (interleukin-4, IL-4)共同增加淋巴细胞免疫球蛋白E (Immunoglobin E,IgE)的产生,在变态反应的迟发相中LTB4又是浸润得炎症细胞:巨噬细胞、中性粒细胞合成分泌的介质,且是I型变态反应迟发相所释放的最经典的炎症介质,在I型变态反应中可引起广泛的炎症损伤。变态反应对机体而言是防御机制的免疫反应,但却会对机体产生伤害性作用。5-羟色胺(5-hydroxytryptamine, serotonin, 5-HT)是炎性介质之一,当体内发生体液性或细胞性免疫反应时,可引起介质的激活或释放,并作用于效应细胞的受体,造成组织损伤,产生炎症反应, 5-羟色胺是I型变态反应迟发相所释放的一种血管活性胺类物质,具有与组胺和过敏性慢反应物质一样收缩平滑肌和增加血管通透性的作用,可引起皮肤红斑、水肿、发绀、出血、瘙痒等炎症反应。白介素-1β(interleukin,IL-1β)是一种主要起免疫调节作用的激素样肽类物质,即炎症前期细胞因子,主要由活化的单核-吞噬细胞产生,释放IL-1β是炎症急性期最基本和最重要的免疫反应现象。本实验通过酶联免疫吸附试验法检测PR患者血清LTB4水平,免疫组织化学技术检测PR患者皮损5-HT、IL-1β表达情况来阐述其在PR发病机制中的作用,并探讨玫瑰糠疹与变态反应的关系。
材料与方法:血清标本均来源于2006年12月~2007年6月到河北医科大学第四附属医院皮肤科就诊的临床诊断为玫瑰糠疹的患者,共30例,其中男性16例,女性14例,年龄15~40岁,平均(24.58±6.19)岁,病程2天~2个月,平均(17.50±14.46)天,并且随机选取10例健康志愿者作为正常对照,对照组在年龄、性别上均与玫瑰糠疹患者组相匹配。所有受检者均无其他LTB4异常的疾病(如呼吸系统疾病、其他过敏性疾病、其他炎症性疾病、自身免疫性疾病等),一个月内无系统用药史(以除外药疹)及冶游史(以除外二期梅毒疹),同时未使用过抗组胺药、抗白三烯药及免疫抑制剂。
皮损标本均来源于2003年3月~2007年5月到河北医科大学第四附属医院皮肤科就诊的玫瑰糠疹患者30例,均经临床和组织病理确诊为玫瑰糠疹,其中男性14例,女性16例,年龄10~42岁,平均(29.73±3.85)岁,病程5~40天,平均(19.89±3.88)天。所有患者均已排除患有其他系统性疾病,且3个月内未接受任何免疫、抗炎及抗过敏治疗。选取河北医科大学第四附属医院外科10例手术患者的健康皮肤作为正常对照,对照组在年龄、性别及取材部位上均与玫瑰糠疹患者相匹配。
应用酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)检测血清LTB4水平,结果采用两独立样本比较的t检验。不同性别的结果亦采用两独立样本比较t的检验,不同年龄及瘙痒程度的结果采用单因素方差分析。取患者皮损区组织做常规组织病理分析,应用免疫组织化学SP法检测5-HT及IL-1β的表达情况,结果采用两等级资料比较的Mann-whiteney U秩和检验以及Spearman等级相关分析。应用SPSS11.5统计软件分析试验结果。
结果
1 ELISA结果
1.1玫瑰糠疹组血清LTB4含量均值1.8632±0.1605,与正常对照组均值1.4484±0.1044比较,经统计学分析,两组间有差异(P﹤0.05)。
1.2不同性别、年龄及瘙痒程度玫瑰糠疹患者血清LTB4含量的均值,经统计学处理,各组间均无差异(P﹥0.05)。
2免疫组化结果
阳性染色为棕黄色颗粒。
2.1 5-HT在玫瑰糠疹皮损表皮中呈阳性表达,主要表达于棘细胞层及颗粒层的细胞浆,30例玫瑰糠疹皮损中,强阳性0例,阳性5例,弱阳性17例,阴性8例,正常表皮不表达,两者差异有显著性(P﹤0.01)。
2.2 IL-1β为阳性细胞浆及胞膜着色,表皮全层广泛阳性着色,30例玫瑰糠疹皮损中,强阳性3例,阳性11例,弱阳性14例,阴性2例,与正常对照组比较明显增高,经统计学分析有差异(P﹤0.05)。
2.3玫瑰糠疹患者皮损中5-HT和IL-1β的表达,经统计学分析,两者有相关性(P﹤0.01)。
结论
1在本实验中,玫瑰糠疹患者组血清LTB4水平升高,提示LTB4可能参与了PR的发生或发展,它的作用可能是通过趋化白细胞向炎症部位聚集并诱导白细胞脱颗粒和产生超氧离子直接造成组织损伤,使白细胞黏附于血管内皮细胞,引起白细胞依赖性的血管通透性增加,与其它致炎因素共同导致了PR的发生发展。LTB4作为I型变态反应迟发相所释放的最经典的炎症介质,提示I型变态反应可能参与了PR的发病过程。
2皮损中5-HT的过度表达,提示PR的发病机制中可能有5-HT的参与。5-HT可能是作为I型变态反应迟发相所释放的血管活性胺类物质,使皮肤毛细血管扩张,通透性增高,引起皮肤红斑等炎症反应,参与了PR患者皮损的发生,亦可能是通过5-HT的其他功能参与了PR皮损的形成和发展。
3 IL-1β在玫瑰糠疹皮损中的过度表达,提示其可能作为一种重要的炎症介质,参与了PR的发病过程,机理可能是促使血管内皮细胞表达内皮细胞-白细胞黏附分子-1和细胞间黏附分子-1,从而增强白细胞与内皮细胞的黏附作用,促进炎细胞渗出与迁移,激活炎细胞,与其它因素共同造成了机体免疫损伤。
4皮损中5-HT和IL-1β的表达,经统计学分析两者有相关性提示其作为致炎因子,可能互相促进共同参与了玫瑰糠疹的发病过程。
Objective: Pityriasis rosea (PR) is an inflammation skin disease, which is common in the Department of Dermatology. The lesions tend to be distributed on the trunk and extremities. The primary macules are yellow-red ,oval or circular and covered with small, thin scales like a collar. The etiology and pathogenesis of PR remain unkown. Now many people consider that it is related with virus infection, hypersensitivity reaction, autoimmunity, genetic anaphylaxis and so on. Leukotrinene B4(leukotriene B4,LTB4)plays an important role in the hypersensitivity,inflammation,and immune system.LTB4 is synthesised immediately by mast cells and basophilic leukocyte degranulate when they are activited and realeased through degranulated way.LTB4 partcipated hypersensitivity reaction through other cells and issues.LTB4 enhances lymphocytes to produce IgE with IL-4 together in typeⅠhypersensitivity early stage, and it is factor synthesized by inflammation cells such as macrophages and neutrophil infiltrated in typeⅠhypersensitivity late stage, it is the classic inflammation factor realeased in typeⅠhypersensitivity late stage. LTB4 can cause wide inflammation in typeⅠhypersensitivity. Hypersensitivity reaction is a protected immune reaction for human body, but witch can hurt the body sometimes.5-hydroxytryptamine is one of inflammatory mediators.When fluids or cells immune is responsed then the meditors are activated or realeased witch hurt the issues through their receptor cell and cause inflammation.5- hydroxytryptamine is one of vasoactive amines material realeased in late stage on typeⅠhypersensitivity ,it can cause smooth muscle shrinkages and increased vascular`s permeability just like histamine and allergic slow-reacting substance. 5-hydroxytryptamine may cause smooth muscle shrinkages, capillaries expansion and enhance the permeability then cause skin erythema, edema, cyanosis, bleeding, itching, and other inflammatory response. IL-1βis an hormone-like peptide substance and its main function is to regulate immune. IL-1βis mainly generated by the activated monocytes– phagocytes. Reased IL-1βis the primary and the most important immune reponse phenomenon. This study detected the serum concentration of IL-1βby ELISA(Enzyme linked immunosorbent assay) and observe the expressions of 5-hydroxytryptamine and IL-1βin PR lesions to explain their function in the pathogenesis of PR. At the same time to explore the relation between PR and hypersensitivity.
Materials and Methods: Thirty PR serum samples includigng 14 males and 16 females were collected from PR patients diagnosed by clinic of the dermatological department of the Forth Affiliated Hospital of Hebei Medical University during Dec,2006 to June,2007. Age ranged from 15 to 40 years(mean 24.58±6.19); Course from 2 days to 2 months,(mean 17.50±14.46). And random select 10 out–hospital healthy volunteers as controls. There are no significant differences in sexes and ages between controls and patients. All patients and volunteers have no LTB4 novel diseases(for example respiratory diseases, other allergic diseases, inflammatory diseases, autoimmune diseases), and had on systematic mediation history as well as swim history (to exclusion durg eruption and PR-type secondary syphilis) within one month, had no taken immunodepressants and antihistamine at the same time.
Thirty lesion case diagnosed as PR clinically and histopathologically were collected from the dermatological department of the Forth Affiliate Hospital of Hebei Medical University during Mar. 2003 to May.2007, who had no other systemic disease or other skin diseases,and had not received any treatment since they were selected. These cases included 14 males and 16 females, age arranged from 10 to 42 years (mean29.73±3.85), course arranged from 5 to 40 days (mean19.89±3.88). The ten normal controls were healthy volunteers in the hospital, and had no significant difference in sex, age and position between patients and controls.
The sera concentration of LTB4 were measured by enzyme linked immunosorbent assay (ELISA), the result were analyzed by 2-independent sample compared T test. The result of gender was analyzed by2-independent sample compared T test and the results of different age and pruritus degree were analyzed by one-factor analysis of variance. The lesion samples were investigated with histopathological method.The levels of 5-HT and IL-1βexpressions were measured by immunohistochemical method. HE-staining was used in histopathology and histostain-SP in immuno-histochemistry. The results were analyzed by Mann-whitney U rand sum test and Spearman’s rank correlation test.
Results
1 ELISA results
1.1 The mean concentrations of sera LTB4 of PR patients and normal controls were1.8632±0.1605, and1.4484±0.1044, compared with each other, there was statistal significance (p<0.05).
1.2 The mean concentrations of sera LTB4 of PR patients, which compared from gender, age phases and pruritus degrees, there were no statistal significance (p>0.05).
2 Immunohistochemistry results Positive staining was submitted Buffy grains.
2.1 5-HT stained on cytoplasm of stratum spinosum and stratum granulosum cell. Among these positive cells, 0 cases (+++), 5cases (++), 17 cases (+), 8 case (-).The level of its expression was markedly increased comparing with the controls (p<0.01).
3.2 IL-1βstained on cell membranes and cytoplasm of full epidermis cell . Among these positive cells, 3 cases (+++), 11cases (++), 14 cases (+), 2 case (-).The level of its expression was markedly increased comparing with the controls (p<0.05).
3.3 There was significant correlation between the expression degree of HSP-70 and TNF-α(p<0.01).
Conclusion
1 In this study, the concentration of serum LTB4 of PR patients is significantly increased, this implies LTB4 participants the development of PR. The mechanism may be LTB4 chemokines leukocyte aggregated to inflammation site and induces leukocyte to degranulate and prduce superoxide ions to hurt issue directly, then make leukocyte adhesion to endothelial cells, increase interleukin-dependent vascular permeability and induce the development of PR with other factors. LTB4 be the classic factor in typeⅠhypersensitivity late stage implies typeⅠhypersensitivity maybe participate the development of PR.
2 The expression of 5-hydroxytryptamine in the lesions is stronger than that of controls , it explains that 5-serotoin may be take part in the development of PR.( It may be vasoactive amines material in typeⅠhypersensitivity late stage cause skin`s capillaries expansion ,permeability enhanced lead the skin emergy erythea and other inflammation reaction to participant the produce of PR It is perhaps that 5-HT takes part in the development of PR by it`s other fuction.
3 The expression of IL-1βin the lesions is stronger than that of controls implies that it be of an important inflammation factors take part in the development of PR.The mechanism maybe IL-1βmake vascular endothelial cells expression endothelial cells-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1,then enhancing the adhesion between interleukins, promoting exudation and migration of inflammatory cells and activating inflammation ,cause the immune hurt to the body with other factors.
4 There was significant correlation between the expression degree of 5-HT and IL-1β,that implies they be of inflammation factors promting eatch other to take part in the development of PR.
材料与方法:血清标本均来源于2006年12月~2007年6月到河北医科大学第四附属医院皮肤科就诊的临床诊断为玫瑰糠疹的患者,共30例,其中男性16例,女性14例,年龄15~40岁,平均(24.58±6.19)岁,病程2天~2个月,平均(17.50±14.46)天,并且随机选取10例健康志愿者作为正常对照,对照组在年龄、性别上均与玫瑰糠疹患者组相匹配。所有受检者均无其他LTB4异常的疾病(如呼吸系统疾病、其他过敏性疾病、其他炎症性疾病、自身免疫性疾病等),一个月内无系统用药史(以除外药疹)及冶游史(以除外二期梅毒疹),同时未使用过抗组胺药、抗白三烯药及免疫抑制剂。
皮损标本均来源于2003年3月~2007年5月到河北医科大学第四附属医院皮肤科就诊的玫瑰糠疹患者30例,均经临床和组织病理确诊为玫瑰糠疹,其中男性14例,女性16例,年龄10~42岁,平均(29.73±3.85)岁,病程5~40天,平均(19.89±3.88)天。所有患者均已排除患有其他系统性疾病,且3个月内未接受任何免疫、抗炎及抗过敏治疗。选取河北医科大学第四附属医院外科10例手术患者的健康皮肤作为正常对照,对照组在年龄、性别及取材部位上均与玫瑰糠疹患者相匹配。
应用酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)检测血清LTB4水平,结果采用两独立样本比较的t检验。不同性别的结果亦采用两独立样本比较t的检验,不同年龄及瘙痒程度的结果采用单因素方差分析。取患者皮损区组织做常规组织病理分析,应用免疫组织化学SP法检测5-HT及IL-1β的表达情况,结果采用两等级资料比较的Mann-whiteney U秩和检验以及Spearman等级相关分析。应用SPSS11.5统计软件分析试验结果。
结果
1 ELISA结果
1.1玫瑰糠疹组血清LTB4含量均值1.8632±0.1605,与正常对照组均值1.4484±0.1044比较,经统计学分析,两组间有差异(P﹤0.05)。
1.2不同性别、年龄及瘙痒程度玫瑰糠疹患者血清LTB4含量的均值,经统计学处理,各组间均无差异(P﹥0.05)。
2免疫组化结果
阳性染色为棕黄色颗粒。
2.1 5-HT在玫瑰糠疹皮损表皮中呈阳性表达,主要表达于棘细胞层及颗粒层的细胞浆,30例玫瑰糠疹皮损中,强阳性0例,阳性5例,弱阳性17例,阴性8例,正常表皮不表达,两者差异有显著性(P﹤0.01)。
2.2 IL-1β为阳性细胞浆及胞膜着色,表皮全层广泛阳性着色,30例玫瑰糠疹皮损中,强阳性3例,阳性11例,弱阳性14例,阴性2例,与正常对照组比较明显增高,经统计学分析有差异(P﹤0.05)。
2.3玫瑰糠疹患者皮损中5-HT和IL-1β的表达,经统计学分析,两者有相关性(P﹤0.01)。
结论
1在本实验中,玫瑰糠疹患者组血清LTB4水平升高,提示LTB4可能参与了PR的发生或发展,它的作用可能是通过趋化白细胞向炎症部位聚集并诱导白细胞脱颗粒和产生超氧离子直接造成组织损伤,使白细胞黏附于血管内皮细胞,引起白细胞依赖性的血管通透性增加,与其它致炎因素共同导致了PR的发生发展。LTB4作为I型变态反应迟发相所释放的最经典的炎症介质,提示I型变态反应可能参与了PR的发病过程。
2皮损中5-HT的过度表达,提示PR的发病机制中可能有5-HT的参与。5-HT可能是作为I型变态反应迟发相所释放的血管活性胺类物质,使皮肤毛细血管扩张,通透性增高,引起皮肤红斑等炎症反应,参与了PR患者皮损的发生,亦可能是通过5-HT的其他功能参与了PR皮损的形成和发展。
3 IL-1β在玫瑰糠疹皮损中的过度表达,提示其可能作为一种重要的炎症介质,参与了PR的发病过程,机理可能是促使血管内皮细胞表达内皮细胞-白细胞黏附分子-1和细胞间黏附分子-1,从而增强白细胞与内皮细胞的黏附作用,促进炎细胞渗出与迁移,激活炎细胞,与其它因素共同造成了机体免疫损伤。
4皮损中5-HT和IL-1β的表达,经统计学分析两者有相关性提示其作为致炎因子,可能互相促进共同参与了玫瑰糠疹的发病过程。
Objective: Pityriasis rosea (PR) is an inflammation skin disease, which is common in the Department of Dermatology. The lesions tend to be distributed on the trunk and extremities. The primary macules are yellow-red ,oval or circular and covered with small, thin scales like a collar. The etiology and pathogenesis of PR remain unkown. Now many people consider that it is related with virus infection, hypersensitivity reaction, autoimmunity, genetic anaphylaxis and so on. Leukotrinene B4(leukotriene B4,LTB4)plays an important role in the hypersensitivity,inflammation,and immune system.LTB4 is synthesised immediately by mast cells and basophilic leukocyte degranulate when they are activited and realeased through degranulated way.LTB4 partcipated hypersensitivity reaction through other cells and issues.LTB4 enhances lymphocytes to produce IgE with IL-4 together in typeⅠhypersensitivity early stage, and it is factor synthesized by inflammation cells such as macrophages and neutrophil infiltrated in typeⅠhypersensitivity late stage, it is the classic inflammation factor realeased in typeⅠhypersensitivity late stage. LTB4 can cause wide inflammation in typeⅠhypersensitivity. Hypersensitivity reaction is a protected immune reaction for human body, but witch can hurt the body sometimes.5-hydroxytryptamine is one of inflammatory mediators.When fluids or cells immune is responsed then the meditors are activated or realeased witch hurt the issues through their receptor cell and cause inflammation.5- hydroxytryptamine is one of vasoactive amines material realeased in late stage on typeⅠhypersensitivity ,it can cause smooth muscle shrinkages and increased vascular`s permeability just like histamine and allergic slow-reacting substance. 5-hydroxytryptamine may cause smooth muscle shrinkages, capillaries expansion and enhance the permeability then cause skin erythema, edema, cyanosis, bleeding, itching, and other inflammatory response. IL-1βis an hormone-like peptide substance and its main function is to regulate immune. IL-1βis mainly generated by the activated monocytes– phagocytes. Reased IL-1βis the primary and the most important immune reponse phenomenon. This study detected the serum concentration of IL-1βby ELISA(Enzyme linked immunosorbent assay) and observe the expressions of 5-hydroxytryptamine and IL-1βin PR lesions to explain their function in the pathogenesis of PR. At the same time to explore the relation between PR and hypersensitivity.
Materials and Methods: Thirty PR serum samples includigng 14 males and 16 females were collected from PR patients diagnosed by clinic of the dermatological department of the Forth Affiliated Hospital of Hebei Medical University during Dec,2006 to June,2007. Age ranged from 15 to 40 years(mean 24.58±6.19); Course from 2 days to 2 months,(mean 17.50±14.46). And random select 10 out–hospital healthy volunteers as controls. There are no significant differences in sexes and ages between controls and patients. All patients and volunteers have no LTB4 novel diseases(for example respiratory diseases, other allergic diseases, inflammatory diseases, autoimmune diseases), and had on systematic mediation history as well as swim history (to exclusion durg eruption and PR-type secondary syphilis) within one month, had no taken immunodepressants and antihistamine at the same time.
Thirty lesion case diagnosed as PR clinically and histopathologically were collected from the dermatological department of the Forth Affiliate Hospital of Hebei Medical University during Mar. 2003 to May.2007, who had no other systemic disease or other skin diseases,and had not received any treatment since they were selected. These cases included 14 males and 16 females, age arranged from 10 to 42 years (mean29.73±3.85), course arranged from 5 to 40 days (mean19.89±3.88). The ten normal controls were healthy volunteers in the hospital, and had no significant difference in sex, age and position between patients and controls.
The sera concentration of LTB4 were measured by enzyme linked immunosorbent assay (ELISA), the result were analyzed by 2-independent sample compared T test. The result of gender was analyzed by2-independent sample compared T test and the results of different age and pruritus degree were analyzed by one-factor analysis of variance. The lesion samples were investigated with histopathological method.The levels of 5-HT and IL-1βexpressions were measured by immunohistochemical method. HE-staining was used in histopathology and histostain-SP in immuno-histochemistry. The results were analyzed by Mann-whitney U rand sum test and Spearman’s rank correlation test.
Results
1 ELISA results
1.1 The mean concentrations of sera LTB4 of PR patients and normal controls were1.8632±0.1605, and1.4484±0.1044, compared with each other, there was statistal significance (p<0.05).
1.2 The mean concentrations of sera LTB4 of PR patients, which compared from gender, age phases and pruritus degrees, there were no statistal significance (p>0.05).
2 Immunohistochemistry results Positive staining was submitted Buffy grains.
2.1 5-HT stained on cytoplasm of stratum spinosum and stratum granulosum cell. Among these positive cells, 0 cases (+++), 5cases (++), 17 cases (+), 8 case (-).The level of its expression was markedly increased comparing with the controls (p<0.01).
3.2 IL-1βstained on cell membranes and cytoplasm of full epidermis cell . Among these positive cells, 3 cases (+++), 11cases (++), 14 cases (+), 2 case (-).The level of its expression was markedly increased comparing with the controls (p<0.05).
3.3 There was significant correlation between the expression degree of HSP-70 and TNF-α(p<0.01).
Conclusion
1 In this study, the concentration of serum LTB4 of PR patients is significantly increased, this implies LTB4 participants the development of PR. The mechanism may be LTB4 chemokines leukocyte aggregated to inflammation site and induces leukocyte to degranulate and prduce superoxide ions to hurt issue directly, then make leukocyte adhesion to endothelial cells, increase interleukin-dependent vascular permeability and induce the development of PR with other factors. LTB4 be the classic factor in typeⅠhypersensitivity late stage implies typeⅠhypersensitivity maybe participate the development of PR.
2 The expression of 5-hydroxytryptamine in the lesions is stronger than that of controls , it explains that 5-serotoin may be take part in the development of PR.( It may be vasoactive amines material in typeⅠhypersensitivity late stage cause skin`s capillaries expansion ,permeability enhanced lead the skin emergy erythea and other inflammation reaction to participant the produce of PR It is perhaps that 5-HT takes part in the development of PR by it`s other fuction.
3 The expression of IL-1βin the lesions is stronger than that of controls implies that it be of an important inflammation factors take part in the development of PR.The mechanism maybe IL-1βmake vascular endothelial cells expression endothelial cells-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1,then enhancing the adhesion between interleukins, promoting exudation and migration of inflammatory cells and activating inflammation ,cause the immune hurt to the body with other factors.
4 There was significant correlation between the expression degree of 5-HT and IL-1β,that implies they be of inflammation factors promting eatch other to take part in the development of PR.
引文
1 王侠生,廖康煌. 杨国亮皮肤病学,第 1 版,上海:上海科学技术文献出版社 2005:518~519
2 Yamaoka KA,Dugsa B,Paul Eugene N et al. Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.Cell mmunol,1994, 156(1)124~134
3 毕爱华 主编 . 医学免疫学,北京:人民军医出版社,1995:184
4 钟华,孙青. 白三烯与特应性皮炎。国外医学皮肤性病学分册,2005,31(5):299~301
5 Bazan JF,Timans JC,Kastelein RA ,et al .A nenly definded interleukin-1? Nature, 1996,379(6566):591
6 赵辨 主编. 临床皮肤病学,第 3 版,南京:江苏科学技术出版社, 2001:775~777
7 Church Antion AT.Case clustering in pityriasia rosea: a mult-icenterpidermiologic study in primary care settings in Hong Kong. Archives of Dermatology, 2003, 139:489~493
8 顾有守.玫瑰糠疹.临床皮肤科杂志. 2006, 35(7)479~480
9 Chuang TY, Perry HO, Hstrup DM et al Recent upper respiratory tract infection and pityriasis rosea a case-cotrol study of 249 matched pairs Br J Dermatol, 1983, 108:587~591
10 Williams JD ,Lee TH ,Lewis RA et al. Intracellutar retention of the 5-lipoxygenase pathway product, leukotriene B4, by human neutuophils activated with unopsonized zymosan.JImmunol, 1985, 134; 2624~2630
11 龚非力 主编. 医学免疫学, 第二版, 北京:科学出版社, 2004:292
12 Skoner D P.Allergic rhinitisi: definition, epidemiology, pathphysiology etection, and diagnosis. J Allergy Clin Immunol, 2001, 108 S2~S8
13 Holt P G,Macaubas C,Stumbles P A,et al.The role of allergy in the development of asthma .Nature , 1999, 402 (6760 Suppl):B12~B17
14 龚非力 主编.医学免疫学,第二版,北京:科学出版社, 2004:293~298
15 Kay AB.Overview of allergy and allergic disease:with aview to the future [1].Br Med Bull, 2000, 56(4):843~864
16 Kageyama Y ,Koide Y,Miyamoto S et al.Leukotriene B4 induced interlukin-1 beta in in synovial cells from patients with rheumatoid arthritis. Scand J Rheumatol, 1994,23 (3):148~150
17 McCain RW ,Holden EP ,Blackwell TR et al. Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesis and release interleukin-8 in vitro.Am J Respir Cell Mol Biol, 1994, 10(6):651~657
18 Yokom izo T,Kato K,Terawarkik, et al.A second leukotriene B4 receptor, BLT2: A new therapeutic target in inflammation and immunological disorders.J Exp Med, 2000, 192:421~431
19 李翠华,王琼,彭振辉等. 荨麻疹患者治疗前后血浆组胺、白三烯 B4 和 5-羟色胺的变化.中华皮肤科杂志,2005, 38(5):312~313
20 林新瑜,段西凌,董巍等 咪唑斯汀治疗慢性荨麻疹疗效观察前后血清白三烯水平检测,临床皮肤科杂志,2005,34(12):856~857
21 钟华 ,郝飞,向明明. 湿疹患者血清和皮损内白三烯水平测定,中华皮肤科杂志,2005, 38(11):702~703
22 于波,程滨珠,吴文育等.玫瑰糠疹皮损中朗格汉斯细胞的超微结构. 复旦学报(医学版), 2006, 33(1):110~112
23 王椿森,李家文.皮肤与性病免疫学. 武汉:湖北科学技术出版社, 1994
24 StulbergDL,WolfreyJ.Pityriasisrosea.AmFamPhysician, 2004, 1, 69(1):87
25 Laberge S,Cruikshank WW,Beer DJ,et al. Secretion of IL-16(lymphocyte chemoattractant factor)from serotonin- stimulated CD8+ Tcells in vitro.J Immunol, 1996, 156:310~315
26 Young MRI,Kut IL,Coogan MP,et al.Stimulation of splenic Tlymphocyte function by endogenous serotonin and by low-dose exogenous serotonin.J Immunol, 1993, 80:395
27 宋智琦,林熙然.某些炎症介质拮抗剂抗过敏作用的实验研究.中国皮肤性病学杂志, 1998, 12(5):266~267
28 Milikan LE, Urticaria. In:Thies BH. Dobson RL. Pathogenesis of skin disease. New York: Churchin Livingstone Inc, 1986:25
29 Pedersen KT, Larsen CG,Ronnevig J.The immunology of contact dermatitis .Contact Deratitis , 1989, 20:81
30 杨钢 主编,内分泌生理与病理生理学,第二版,天津科技出版社, 2000 年, 335
31 李明华,殷凯生,蔡映云. 哮喘病学 第 2 版 80 页
32 王爱学,李玉平等. 玫瑰糠疹表皮内血管细胞粘附分子 1和细胞间黏附分子 1 的表达.临床皮肤科杂志, 2006, 35(2):77~78
33 Aiba S Tagami H Immunohistologic studies in pityriasis roea. Evidence for cellar immune reaction in the lesional epidermis, Arch Dermatol, 1985, 12(16):761~765
34 刘炜 ,赵庆利,Reno Debets,蔡瑞康等.白介素-1β 诱导正常人皮肤表达银屑病免疫病理表型.中华皮肤科杂志, 1999, 32(2):106~108
35 金惠铭, 卢急案,殷建华. 细胞分子与病理生理学,第 1版,河南 郑州大学出版社,2002:417~430
1 Zipser RD, Laffi G. Prostaglandins, thromboxanes and leukotrienes in clinical medicine.West J Med, 1985, 143: 485~497
2 Crooks SW,Stockley RA. Moleules in focus Leukotriene B4.Int J B iochem Cell Biol, 1998, 30: 175~178
3 林耀广 主编 现代哮喘病学, 第一版, 北京: 中国协和 医科大学出版社, 2004: 213~214
4 Williams JD ,Lee TH ,Lewis RA et al. Intracellutar retention of the 5-lipoxygenase pathway product,leukotriene B4 ,by human neutuophils activated with unopsonized zymosan.J Immunol, 1985, 134; 2624~2630
5 Yamaoka KA,Dugsa B ,Paul Eugene N et al. Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.Cell Immunol, 1994, 156(1) 124~124
6 毕爱华 主编. 医学免疫学,北京:人民军医出版社,1995: 184~187
7 Kageyama Y ,Koide Y,Miyamoto S et al.Leukotriene B4 induced interlukin-1 beta in in synovial cells from patients with rheumatoid arthritis. Scand J Rheumatol, 1994,23(3): 148~150
8 McCain RW ,Holden EP ,Blackwell TR et al. Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesis and release interleukin-8 in vitro.Am J Respir Cell Mol Biol, 1994, 10(6): 651~657
9 Milano S, Arcoleo F ,Diel M et al.Ex vivo evidence for PGE2 and LTB4 involvement in cutaneous eishmaniasis:relation with infection status and cytokine production.Parasitology, 1996, 112(part1): 13~19
10 Arcoleo F ,Milano S ,D’Agositino P et al.Effect of exogenous leuktriene B4 on BSLB/C mice splenocyte production of Th1 and Th2 lymphokines. Int J Immunopharmacol, 1995, 17(6): 457~463
11 Yokom izo T,Kato K,Terawarkik,etal.A second leukotriene B4 receptor,BLT2:A new therapeutic target in inflammation and immunological disorders. J Exp Med, 2000, 192: 421~431.
12 Wedi B ,Kapp A .Pathophysiological role of leukotrienes in dematological disease : potential the rapeutic implications, Bio Drugs, 2001, 15:729~743
13 Taskapan MO. Zileuton and atopic dermatitis dermatitis JAnn Allergy Asthma Immunol, 2001, 87(2): 162~163
14 Koro O, Furutani K ,Hide M, et al Chemical mediators in atopic dermatitis involvement of leukotriene B4 released by a type Iallergic reaction in the pathogenesis of atopic dermatitis J Allergy Clin Immunol , 1999, 103: 663~670
15 Adamek-Guzik T,Guzik TJ,Czeiniawska-Mysik G,et al Urinary leukotriene levels are increased during exacerbationof atopic eczema/dermatitis syndrome.Relation to clinical status Allergy, 2002, 57: 732~736
16 李翠华 ,王琼 ,彭振辉等. 荨麻疹患者治疗前后血浆组胺、白三烯B4和5-羟色胺的变化, 中华皮肤科杂志,2005,38(5):312~313
17 林新瑜, 段西凌 ,董巍等 咪唑斯汀治疗慢性荨麻疹疗效观察前后血清白三烯水平检测,临床皮肤科杂志,2005,34(12):856~857
18 Maltby NH,J Ind PW,Causon RC ,et al .Leukotriene E4 release in cold uritcaria.Clin Exp Allergy, 1989, 19(1): 33~ 36
19 Wedi B, Novacovic V,Koerner M,et al .Chronic urticaria serum induces histamine release, leukotriene production ,and basophil CD63 surface expression–inhibitory effects of anti-inflammatory drugs,J Allergy Clin Immunol, 2000, 105(3): 552~560
20 钟华,郝飞,向明明. 湿疹患者血清和皮损内白三烯水平测定,中华皮肤科杂志,2005,38(11): 702~703
21 Kawans S Ueno A, Nishiyama S .Increased levels ofimmunoreactive leukotriene B4 in blister fluids of bullous pemphigoid patients and effects of a selective 5-lipoxygenase inhibitor on experimental skin lisions, Acta Derm Venereol , 1990, 70(4): 281~285
22 Cetkovska P,Pizinger K . Childhood pemphigus associated With montelukast administration,Clin Exp Dermatol, 2003, 28(3): 328~329
23 Hackshaw KV,Voelkel NF, Thomas RB,et al Urine leukotriene E4 levles are elevated in patients with active systemic lupus Erythermatosus,J Rheumatol, 1992, 19(2): 252~258
24 Hackshaw KV, Shi Y , Brandwein SR. et al A pilot study of zileuton, a novel selective 5-lipoxygenase inhibitor in patients with systemic lupus erythematosus , J Rheumatol , 1995, 22(3): 462~468
25 Nakamura K,Imakado S, Takizawa M,et al. Exacerbation of metals accompanied by elevated levels of leukotriene B4 in pustules. J Am Acad Dermatol, 2000, 42: 1021~1025
26 Valacer DJ. New treatments for ashthma: the role of leukotriene modifier agents. J Natl Med Assoc.1999, 91: 26S~39S
27 Wedi B, KappA. Pathophysiological role of leukotrienes in dematological disease: potential the rapeutic implications, Biodrugs, 2001, 15: 729~743
28 Yanase DJ, David-Bajar K.The Leukotriene antagonist montelukast as a therapeutic agent for atopic dermatitis.J AmAcad Dermatol, 2001, 44: 89~93
29 Pei AY,Chan HH,Leung TF.Montelukast in the treatment of children with moderate-to-severe atopic dermatitis: a pilot study.Pediatr Allergy Immunol, 2001, 12: 154~158
30 Concha del Rio LE,Arroyave CM. A leukotriene antagonist(montelukast) in the treatment of atopic dermatitis in pediatric patients.Rev Alerg Mex, 2003, 50: 187~191
31 Carucci JA, Washenik K,Weinstein A,et al. he leukotriene antagonist zafirlukast as a therapeutic agent for atopic dermatitis. Arch Dermatol, 1998, 134: 785~786
32 Zabawski EJ Jr,Kahn MA,Gregg LJ. Treatment of aptoic dermatitis with zafirlufast.Dermatol Online J,1999, 5: 10
33 Bagenstose SE,Levin L,Bemstein in JA. The addition of zafirlukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test result. J Allergy Clin Immunol, 2004, 113: 134~140
34 Bonadonna P,Lombardi C, Senna G,et al.Treatment of acquired cold uricaria with cetirizine and zafirlukast in combination. J Am Acad Dematol, 2003, 49: 714~716
35 Nomura A, Fujisawa H, Sekizawa K. Treatment of bullous pemphigoid with a leukotriene receptor antagonist, Allergy, 2003, 58(2): 162~163
36 Woodmansee DP, Simon RA. A pilot study examining the role of zieuton in atopic dermatitis. Ann Allergy Asthma Immunol, 1999, 83: 548~552
37 Wenzel SE, Kamada AK, Zileuton:the first 5-lipoxygenaseInhibitor for the treatment of asthma Ann Phamcother, 1996, 30: 858~864
38 Zemtsov A,Bucchino S,Mcdowell MR. Potential use of leukotriene inhibitors in treatment of psoriasis. Dematology, 2003, 206: 179~180
39 孙连文摘,郑家润校, 预测应用白三烯 B4 抑制治疗皮肤病的潜力, 国外医学皮肤性病学分册,2001,27(3):186
2 Yamaoka KA,Dugsa B,Paul Eugene N et al. Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.Cell mmunol,1994, 156(1)124~134
3 毕爱华 主编 . 医学免疫学,北京:人民军医出版社,1995:184
4 钟华,孙青. 白三烯与特应性皮炎。国外医学皮肤性病学分册,2005,31(5):299~301
5 Bazan JF,Timans JC,Kastelein RA ,et al .A nenly definded interleukin-1? Nature, 1996,379(6566):591
6 赵辨 主编. 临床皮肤病学,第 3 版,南京:江苏科学技术出版社, 2001:775~777
7 Church Antion AT.Case clustering in pityriasia rosea: a mult-icenterpidermiologic study in primary care settings in Hong Kong. Archives of Dermatology, 2003, 139:489~493
8 顾有守.玫瑰糠疹.临床皮肤科杂志. 2006, 35(7)479~480
9 Chuang TY, Perry HO, Hstrup DM et al Recent upper respiratory tract infection and pityriasis rosea a case-cotrol study of 249 matched pairs Br J Dermatol, 1983, 108:587~591
10 Williams JD ,Lee TH ,Lewis RA et al. Intracellutar retention of the 5-lipoxygenase pathway product, leukotriene B4, by human neutuophils activated with unopsonized zymosan.JImmunol, 1985, 134; 2624~2630
11 龚非力 主编. 医学免疫学, 第二版, 北京:科学出版社, 2004:292
12 Skoner D P.Allergic rhinitisi: definition, epidemiology, pathphysiology etection, and diagnosis. J Allergy Clin Immunol, 2001, 108 S2~S8
13 Holt P G,Macaubas C,Stumbles P A,et al.The role of allergy in the development of asthma .Nature , 1999, 402 (6760 Suppl):B12~B17
14 龚非力 主编.医学免疫学,第二版,北京:科学出版社, 2004:293~298
15 Kay AB.Overview of allergy and allergic disease:with aview to the future [1].Br Med Bull, 2000, 56(4):843~864
16 Kageyama Y ,Koide Y,Miyamoto S et al.Leukotriene B4 induced interlukin-1 beta in in synovial cells from patients with rheumatoid arthritis. Scand J Rheumatol, 1994,23 (3):148~150
17 McCain RW ,Holden EP ,Blackwell TR et al. Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesis and release interleukin-8 in vitro.Am J Respir Cell Mol Biol, 1994, 10(6):651~657
18 Yokom izo T,Kato K,Terawarkik, et al.A second leukotriene B4 receptor, BLT2: A new therapeutic target in inflammation and immunological disorders.J Exp Med, 2000, 192:421~431
19 李翠华,王琼,彭振辉等. 荨麻疹患者治疗前后血浆组胺、白三烯 B4 和 5-羟色胺的变化.中华皮肤科杂志,2005, 38(5):312~313
20 林新瑜,段西凌,董巍等 咪唑斯汀治疗慢性荨麻疹疗效观察前后血清白三烯水平检测,临床皮肤科杂志,2005,34(12):856~857
21 钟华 ,郝飞,向明明. 湿疹患者血清和皮损内白三烯水平测定,中华皮肤科杂志,2005, 38(11):702~703
22 于波,程滨珠,吴文育等.玫瑰糠疹皮损中朗格汉斯细胞的超微结构. 复旦学报(医学版), 2006, 33(1):110~112
23 王椿森,李家文.皮肤与性病免疫学. 武汉:湖北科学技术出版社, 1994
24 StulbergDL,WolfreyJ.Pityriasisrosea.AmFamPhysician, 2004, 1, 69(1):87
25 Laberge S,Cruikshank WW,Beer DJ,et al. Secretion of IL-16(lymphocyte chemoattractant factor)from serotonin- stimulated CD8+ Tcells in vitro.J Immunol, 1996, 156:310~315
26 Young MRI,Kut IL,Coogan MP,et al.Stimulation of splenic Tlymphocyte function by endogenous serotonin and by low-dose exogenous serotonin.J Immunol, 1993, 80:395
27 宋智琦,林熙然.某些炎症介质拮抗剂抗过敏作用的实验研究.中国皮肤性病学杂志, 1998, 12(5):266~267
28 Milikan LE, Urticaria. In:Thies BH. Dobson RL. Pathogenesis of skin disease. New York: Churchin Livingstone Inc, 1986:25
29 Pedersen KT, Larsen CG,Ronnevig J.The immunology of contact dermatitis .Contact Deratitis , 1989, 20:81
30 杨钢 主编,内分泌生理与病理生理学,第二版,天津科技出版社, 2000 年, 335
31 李明华,殷凯生,蔡映云. 哮喘病学 第 2 版 80 页
32 王爱学,李玉平等. 玫瑰糠疹表皮内血管细胞粘附分子 1和细胞间黏附分子 1 的表达.临床皮肤科杂志, 2006, 35(2):77~78
33 Aiba S Tagami H Immunohistologic studies in pityriasis roea. Evidence for cellar immune reaction in the lesional epidermis, Arch Dermatol, 1985, 12(16):761~765
34 刘炜 ,赵庆利,Reno Debets,蔡瑞康等.白介素-1β 诱导正常人皮肤表达银屑病免疫病理表型.中华皮肤科杂志, 1999, 32(2):106~108
35 金惠铭, 卢急案,殷建华. 细胞分子与病理生理学,第 1版,河南 郑州大学出版社,2002:417~430
1 Zipser RD, Laffi G. Prostaglandins, thromboxanes and leukotrienes in clinical medicine.West J Med, 1985, 143: 485~497
2 Crooks SW,Stockley RA. Moleules in focus Leukotriene B4.Int J B iochem Cell Biol, 1998, 30: 175~178
3 林耀广 主编 现代哮喘病学, 第一版, 北京: 中国协和 医科大学出版社, 2004: 213~214
4 Williams JD ,Lee TH ,Lewis RA et al. Intracellutar retention of the 5-lipoxygenase pathway product,leukotriene B4 ,by human neutuophils activated with unopsonized zymosan.J Immunol, 1985, 134; 2624~2630
5 Yamaoka KA,Dugsa B ,Paul Eugene N et al. Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.Cell Immunol, 1994, 156(1) 124~124
6 毕爱华 主编. 医学免疫学,北京:人民军医出版社,1995: 184~187
7 Kageyama Y ,Koide Y,Miyamoto S et al.Leukotriene B4 induced interlukin-1 beta in in synovial cells from patients with rheumatoid arthritis. Scand J Rheumatol, 1994,23(3): 148~150
8 McCain RW ,Holden EP ,Blackwell TR et al. Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesis and release interleukin-8 in vitro.Am J Respir Cell Mol Biol, 1994, 10(6): 651~657
9 Milano S, Arcoleo F ,Diel M et al.Ex vivo evidence for PGE2 and LTB4 involvement in cutaneous eishmaniasis:relation with infection status and cytokine production.Parasitology, 1996, 112(part1): 13~19
10 Arcoleo F ,Milano S ,D’Agositino P et al.Effect of exogenous leuktriene B4 on BSLB/C mice splenocyte production of Th1 and Th2 lymphokines. Int J Immunopharmacol, 1995, 17(6): 457~463
11 Yokom izo T,Kato K,Terawarkik,etal.A second leukotriene B4 receptor,BLT2:A new therapeutic target in inflammation and immunological disorders. J Exp Med, 2000, 192: 421~431.
12 Wedi B ,Kapp A .Pathophysiological role of leukotrienes in dematological disease : potential the rapeutic implications, Bio Drugs, 2001, 15:729~743
13 Taskapan MO. Zileuton and atopic dermatitis dermatitis JAnn Allergy Asthma Immunol, 2001, 87(2): 162~163
14 Koro O, Furutani K ,Hide M, et al Chemical mediators in atopic dermatitis involvement of leukotriene B4 released by a type Iallergic reaction in the pathogenesis of atopic dermatitis J Allergy Clin Immunol , 1999, 103: 663~670
15 Adamek-Guzik T,Guzik TJ,Czeiniawska-Mysik G,et al Urinary leukotriene levels are increased during exacerbationof atopic eczema/dermatitis syndrome.Relation to clinical status Allergy, 2002, 57: 732~736
16 李翠华 ,王琼 ,彭振辉等. 荨麻疹患者治疗前后血浆组胺、白三烯B4和5-羟色胺的变化, 中华皮肤科杂志,2005,38(5):312~313
17 林新瑜, 段西凌 ,董巍等 咪唑斯汀治疗慢性荨麻疹疗效观察前后血清白三烯水平检测,临床皮肤科杂志,2005,34(12):856~857
18 Maltby NH,J Ind PW,Causon RC ,et al .Leukotriene E4 release in cold uritcaria.Clin Exp Allergy, 1989, 19(1): 33~ 36
19 Wedi B, Novacovic V,Koerner M,et al .Chronic urticaria serum induces histamine release, leukotriene production ,and basophil CD63 surface expression–inhibitory effects of anti-inflammatory drugs,J Allergy Clin Immunol, 2000, 105(3): 552~560
20 钟华,郝飞,向明明. 湿疹患者血清和皮损内白三烯水平测定,中华皮肤科杂志,2005,38(11): 702~703
21 Kawans S Ueno A, Nishiyama S .Increased levels ofimmunoreactive leukotriene B4 in blister fluids of bullous pemphigoid patients and effects of a selective 5-lipoxygenase inhibitor on experimental skin lisions, Acta Derm Venereol , 1990, 70(4): 281~285
22 Cetkovska P,Pizinger K . Childhood pemphigus associated With montelukast administration,Clin Exp Dermatol, 2003, 28(3): 328~329
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