初次变应性接触性皮炎小鼠模型的建立与评价

目的 建立并评价初次变应性接触性皮炎（ACD）小鼠模型。方法 用1-氟-2,4二硝基苯（DNFB）分别制作经典ACD小鼠模型及初次ACD模型,在以下3方面对二者进行比较：以激发前后耳肿度为临床观察指标;以ELISA与实时RT-PCR方法检测耳组织中IL-2、INF-γ与IL-4的表达水平;进行局部淋巴结分析（LLNA）,以流式细胞术检测耳引流淋巴结中淋巴细胞增殖与活化的情况。结果 初次ACD小鼠模型耳背部单次用药6天后出现较明显的耳肿度变化,这与经典ACD模型自诱导至炎症出现的时间相同;与经典ACD小鼠模型相似,初次ACD小鼠模型的耳肿度亦呈现出随时间变化的趋势;二者组织浸润细胞均以单一核细胞为主;与正常小鼠相比,二者组织中Th1型细胞因子IL-2与IFN-γ表达均增加,Th2型因子IL-4均未增加,耳引流淋巴结中T淋巴细胞均出现明显增殖与活化。结论 初次ACD模型与经典模型机制相似,均为Th1型变态反应,二者可以互用。     

咪唑斯汀抑制小鼠变应性接触性皮炎机制的研究

目的 研究咪唑斯汀对小鼠变应性接触性皮炎(ACD)的抑制作用,探讨其作用机理.方法 建立小鼠ACD模型,观察口服不同剂量咪唑斯汀对小鼠耳肿胀的抑制作用.采用ELISA法检测ACD小鼠产生干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)和白介素4(IL-4)的水平及咪唑斯汀对这3种细胞因子的作用.结果 口服各剂量咪唑斯汀均能明显抑制ACD小鼠耳肿胀(P<0.05);ACD小鼠血清及脾淋巴细胞IFN-γ水平均明显升高(P<0.01).ACD小鼠血清TNF-α水平明显升高(P<0.01),腹腔巨噬细胞产生TNF-α水平无明显变化(P>0.05).ACD小鼠血清及脾淋巴细胞产生IL-4水平无明显变化(P>0.05).不同剂量咪唑斯汀对3种细胞因子均有显著或不同程度的抑制作用.结论 咪唑斯汀对小鼠ACD疗效可能通过其对细胞因子的抑制而发挥作用.     

四种中药复方对小鼠实验性皮炎作用的研究

目的　为了探讨中医治则和方剂组成与治疗湿疹有关的实验药效学作用之间的关系。方法　利用小鼠二硝基氟苯变应性接触性皮炎动物模型 ,以具有抑制Ⅳ型变态反应的中药 ,组成 4个不同的复方 ,进行动物实验。结果　兼有凉血活血、清热祛风、利湿多种功效的Ⅲ方 (赤芍、栀子、荆芥、浮萍、茯苓 )作用最好 ,并显示诱发皮炎后小鼠血浆降钙素基因相关肽降低 ,投与中药可对此具有上调的作用。结论　按中医理法选用具有抑制Ⅳ型变态反应的中药组方可在临床中进行验证     

变应性接触性皮炎与免疫耐受

变应性接触性皮炎以T细胞介导的Ⅳ型变态反应为主，少部分也可表现为I型变态反应的迟发相。机体的免疫系统一方面对抗外来的病原体和致敏原，同时发挥调节功能，控制过强的免疫反应，临床出现免疫耐受。Ⅳ型变态反应的免疫调节基础是CD4^＋的T调节细胞，在变应性接触性皮炎中发挥调节作用的主要为1型T调节细胞和2型T调节细胞。T调节细胞已成为免疫治疗及其评价的分子标记之一。     

变应性接触性皮炎体外实验的研究进展

斑贴试验是诊断变应性接触性皮炎病因的金标准,但尚存在一定缺陷,如操作繁琐,判读存在一定的主观性,试验过程需受试者往返2～3次等.体外实验与斑贴试验相比,客观、安全.目前体外实验方法主要有淋巴细胞转化试验、细胞因子释放试验、细胞活化标志物检测及其他的改进试验等,多通过检测淋巴细胞功能来鉴别过敏个体与非过敏个体.这些方法各有利弊,多处于实验室探索阶段,要用于临床仍需更进一步的研究.     

香料变应性接触性皮炎

香料(fragrance)是一种能被嗅觉嗅出香气或味觉尝出香味的物质,广泛存在于化妆品、调味剂、清洁剂、药物以及多种生活用品中^[1,2].随着芳香产品的广泛应用,香料所引起的接触变态反应日益受到人们的重视.     

变应性接触性皮炎中细胞因子的表达

变应性接触性皮炎是常见的迟发型变态反应性皮肤病,细胞因子的表达在该病的发病过程中起重要作用。其中肿瘤坏死因子-α与白介素-1β主要在变应性接触性皮炎的诱导致敏阶段促使朗格汉斯细胞向局部淋巴结的聚集和抗原的提呈,干扰素-γ和白介素-4是变应性接触性皮炎效应阶段主要的一对具有相互拮抗作用的细胞因子,还有其他一些细胞因子在变应性接触性皮炎中起作用。多种细胞因子共同影响变应性接触性皮炎的发生、发展和转归。     

变应性接触性皮炎免疫学发病机制研究进展

变应性接触性皮炎发病机制非常复杂,近来研究有新的发现,其中表皮角质形成细胞除促进T细胞的浸润外,还有限制该病发展的作用;皮肤树突细胞除执行抗原提呈作用外,可能还有免疫调节作用.还发现有新的免疫细胞和分子参与作用,如CD4+CD25+Foxp3+T细胞在其中发挥免疫抑制功能;Th17细胞介导、促进炎症反应;B10细胞通过IL-10依赖机制有负调节作用.一些黏附分子及其配基(PSGL-1等)和趋化因子(CCL21等)在发病中也起着一定作用.

Abstract：

The pathogenesis of allergic contact dermatitis (ACD) is very complicated. However, new discoveries have been made on the topic in recent studies. Epidermal keratinocytes not only promote T cell infiltration, but also limit the development of ACD. In addition, cutaneous dendritic cells possess both antigen presenting function and immunomodulatory activity. Furthermore, some immune cells and molecules have been newly demonstrated to be involved in the pathogenesis. For example, CD4+ CD25+ Foxp3+ T cells play a powerful immunosuppression role; T helper 17 (Th17) cells mediate and enhance inflammation reaction; B10 cells play a negative regulatory effect via an interleukin (IL)-10-dependent mechanism. Some adhesion molecules and their ligand (such as PSGL-1), as well as chemokines (such as CCL21) also exert a certain role in the pathogenesis of ACD.     

免疫调节剂治疗变应性接触性皮炎的进展

随着变应性接触性皮炎的发病机制和病理生理过程认识的深入，应用免疫调节剂治疗该病的研究也逐渐深入。磷酸二酯酶-4抑制剂通过调节细胞因子而抑制炎症反应。子囊霉素衍生物与糖皮质激素相比，治疗效果相同或更优，但不良反应更小。来氟米特、麦考酚酯的免疫抑制机制类似，疗效明确。免疫调节剂的上述作用，使其有望成为治疗变应性接触性皮炎的新选择。     

肥大细胞在变应性接触性皮炎发病中的作用进展

变应性接触性皮炎（ACD）是由接触性变应原引起的T细胞介导的炎症性皮肤病,肥大细胞在其中的作用尚存在争议。在致敏阶段,肥大细胞通过释放炎症因子促进中性粒细胞募集发挥促炎作用,通过刺激或抑制树突细胞的迁移影响致敏过程。在激发阶段,肥大细胞促进非变应原特异性炎症;增强中度,但是抑制重度及慢性ACD的变应原所致特异性炎症。除...     

Occupational allergic contact dermatitis from drugs in healthcare workers

Contact sensitivity to drugs administered systemically occurs mainly among healthcare workers, pharmaceutical operatives, and veterinary surgeons. Of the 14,689 patients suspected of contact allergy examined in our department from 1978 to 2001, occupational allergic contact dermatitis from drugs in healthcare workers was diagnosed in 33, the first in 1980. The most common sensitizers were antibiotics such as penicillins, cephalosporins, and aminoglycosides. They accounted altogether for 35 positive patch tests, followed by propacetamol hydrochloride, and ranitidine hydrochloride, which elicited 10 and 7 positive reactions, respectively. The aim of this report is to draw attention to the importance of occupational contact allergy to drugs in healthcare workers. By far the greatest number of the sensitized patients in this series were nurses, there being 26 nurses, 4 veterinarians, 2 pharmacists, and 1 medical doctor.     

Inhibition of allergic contact dermatitis to DNCB but not to oxazolone in interleukin-4-deficient mice

The role of interleukin-4 as a regulator of immune responses in the skin is investigated with regard to the outcome of contact hypersensitivity reaction in interleukin-4-deficient BALB/C mice. In previous studies conflicting results were obtained concerning the role of interleukin-4 in contact hypersensitivity reactions supporting either a proinflammatory or rather an inhibitory function of this cytokine. Interleukin-4 deficient BALB/C mice sensitized to 2,4-dinitrochlorobenzene showed after challenge a significant reduction in magnitude and duration of the contact hypersensitivity response in comparison with wild-type mice. This attenuation was accompanied by a significant reduction of edema and cellular infiltrates in the dermis and a lacking induction of IL-10 mRNA expression in skin. Also, adoptive transfer experiments revealed that BALB/C mice failed to exhibit contact hypersensitivity after injection of lymph node cells obtained from sensitized interleukin-4 deficient mice. To examine further the role of the contact allergen used to induce the contact hypersensitivity response, mice were also sensitized and challenged with Oxazolone. Here a similar magnitude and duration of contact hypersensitivity in both the interleukin-4 deficient mice and BALB/C control mice was observed. This indicates that the contact hypersensitivity response to 2,4-dinitrochlorobenzene and Oxazolone may partly evolve on different pathways being dependent and independent of interleukin-4. Our results clearly show that the complete loss of endogenous interleukin-4 expression in BALB/C mice is associated with an impaired manifestation of contact hypersensitivity response to 2,4-dinitrochlorobenzene, implying an important proinflammatory function of this cytokine.     

饱和氢氯化钠溶液对小鼠变应性接触性皮炎的影响

目的 探讨饱和氢氯化钠溶液对变应性接触性皮炎（ACD）的治疗作用及相关机制。方法 将40只小鼠随机分为四组：对照组、对照 + 饱和氢氯化钠溶液组、ACD组和ACD + 饱和氢氯化钠溶液组。将二硝基氟苯搽在小鼠外耳建立二硝基氟苯致小鼠变应性接触性皮炎模型,腹腔注射饱和氢氯化钠溶液5 ml/kg进行治疗。评估皮损,计算耳厚度差、耳肿胀度,酶联免疫吸附试验检测皮损组织肿瘤坏死因子α（TNF-α）、白介素（IL）-6、IL-17和干扰素γ（IFN-γ）水平,并计数皮损中炎性细胞数量。采用SPSS 18.0统计软件进行数据分析,各组间比较采用单因素方差分析,两两比较采用LSD分析法。 结果 与对照组比较,ACD组皮损评分（7.33 ± 1.53）、耳厚度差［（0.73 ± 0.15） mm］和耳肿胀度［（18.67 ± 3.05） mg］增加,左耳皮损组织TNF-α［（1475.52 ± 233.81） ng/g］、IL-6［（184.65 ± 78.39） ng/g］、IL-17［（628.56 ± 201.44） ng/g］和IFN-γ［（197.72 ± 37.81） ng/g］水平和炎性细胞数量［（752.00 ± 166.06）个/mm2］亦增加（均P < 0.05）;与ACD组比较,ACD + 饱和氢氯化钠溶液组皮损评分（3.33 ± 0.58）、耳厚度差［（0.46 ± 0.11） mm］、耳肿胀度［（11.00 ± 2.64） mg］、左耳皮损组织TNF-α［（817.72 ± 101.13） ng/g］、IL-6［（95.86 ± 36.65） ng/g］、IL-17［（373.38 ± 126.74） ng/g］和IFN-γ［（63.31 ± 17.38） ng/g］水平和炎性细胞数量［（384.00 ± 97.35）个/mm2］均降低（均P < 0.05）。结论 饱和氢氯化钠可以减轻ACD中炎症因子的释放。     

Occupational allergic contact dermatitis caused by isocyanates

Between 1978 and 2001, 22 patients were diagnosed with occupation-related allergic contact dermatitis from isocyanates and/or polyurethanes in our clinic. 13 had a positive reaction to the isocyanates, of whom 10 also reacted to diaminodiphenylmethane (MDA), which is used in the production or processing of isocyanates and polyurethanes; 9 reacted only to MDA. The object of the present study was to identify the trades and industries responsible for the development of contact allergy to these resins. Such patients must be patch tested with the isocyanates contacted at work, and account must be taken of positive reactions to MDA as a marker for isocyanate sensitivity.