摘要
药疹是药物通过内服、吸入等途径进入人体，在皮肤、粘膜上引起的炎症，严重者可累及机体的各个系统，甚至导致死亡。近年来，该病的发病率正逐步上升，影响了人们的身体健康和生活质量。发疹型药疹、大疱性表皮坏死松解型药疹的发病机理至今尚未完全清楚，国内外很多学者研究其发病机理，提出细胞因子在发疹型药疹、大疱性表皮坏死松解型药疹中起重要作用。本文所研究的TNF-α、IL-8是属于炎性介质家族的成员，我们对TNF-α、IL-8在发疹型药疹、大疱性表皮坏死松解型药疹发病机理中的作用进行了研究。
目的：本研究利用双抗体夹心ELISA法分别测定26例用药未发生药疹的患者、30例健康人、50例发疹型患者、8例大疱性表皮坏死松解型药疹患者血清中TNF-α、IL-8的含量，试验组与对照组TNF-α、IL-8含量进行比较。并动态分析了病程中不同时间其含量的变化，以探讨TNF-α、IL-8在发疹型药疹、大疱性表皮坏死松解型药疹发生、转归中的作用，为临床治疗提供理论依据。
方法：选择2001~2003年吉林大学第二医院、辽源市医院门
诊及住院的药疹患者58例，近两周内未用过皮质类固醇激素、免疫抑制剂和抗组胺药。均取早晨空腹静脉血3ml，保存于-25℃待测。
统计学方法：发疹型药疹、大疱性表皮坏死松解型药疹组治疗前后TNF-α、IL-α水平分别与对照组比较，采用t检验。
结果：1、试验组与对照组TNF-α的检测结果：发疹型药疹患者组在发病第1周时取静脉血的50例，第2周时取静脉血的32例，第4周取静脉血的15例，与对照A组B组分别比较，t值分别为15.43和18.68，p均<0.01；第1周取静脉血分别与两对照组比较，t值分别为15.43和18.69; 第2周取静脉血分别与两对照组比较，t值分别为12.67和16.34，p均<0.01；第4周取静脉血与对照组A组比较，t=8.65，p<0.01；而与对照B组比较，t=2.91，p>.05；大疱性表皮坏死松解型药疹组在第1周取静脉血8例，第2周取静脉血8例，第3周取静脉血5例，第4周取静脉血5例，经t检验，p<0.01（t由第一~四周分别为14.97、15.33、2.79）差异有显著性。对照组A与B组血清中TNF-α水平经t检验t=0.39 P>0.05，差异无显著性。
2、试验组与两对照组IL-8的检测结果，对照A组与对照B
组血清IL-8水平经t检验t=0.39，p>.05，差异无显著性。发疹型药疹患者第1周取静脉血分别与对照组比较，t值分别为22.49和27.91，p均<0.01；第2周取静脉血与两对照组比较，t值分别为33.16和14.1，p均<0.01；第4周取静脉血与两对照A组比较，t=11.34，p<0.01；而与对照B组比较t=0.41，p>.05；大疱性表皮坏死松解药疹患者组各周患者分别于对照组A、B比较，经t检验，P均小于0.01，差异有显著性。第1周患者与第2周患者，第2周与第3周患者，第3周与第4周患者相比较，经t检验，P均<0.01（t值分别为8.79、3.04、2.42），差异有显著性。
讨论：药疹的发病机理复杂，研究证实，免疫异常与药疹的皮损炎症的发生、发展有密切关系。TNF-α是一种单核因子，主要是由单核细胞和巨噬细胞产生，能提高中性粒细胞的吞噬能力，增加过氧阴离子的产生，增强ADCC功能，刺激细胞脱颗粒和分泌髓过氧化物酶，导致细胞坏死、组织损伤，增强超敏反应，TNF-α在体内细胞因子网络系统中起重要作用，其含量增加可引起IL-1、IL-8、IL-6、IFN等细胞因子含量发生变化，导致细胞因子网络系统失衡，进一步使机体发生病理生理改变，导致发疹型药疹、大疱表皮松解型药疹的皮损的炎症的反应。
我们采用试验组与正常组对照的方法及治疗前后对比的方法，动态观察TNF-α在发疹型药疹、大疱表皮松解型药疹的发病、转归中的作用，结果显示，治疗前TNF-α含量明显高于治疗后的血清中的含量。并且与疾病严重程度有关。且含量随着病情的好转而降低，与正常对照组比较，p<0.01，差异极显著，这证明TNF-α在发疹型药疹、大疱性表皮坏死松解型药疹的发病过程中起重要作用。
IL-8进入血循环，对中性粒细胞有很强的趋化作用，促进炎症细胞聚集及浸润，损伤局部组织，参与免疫调节和炎症反应，因此与发疹型药疹、大疱性表皮坏死松解型药疹这一炎症性疾病密切相关。
我们采用治疗组与正常组对照的方法及治疗前后对比的方法观察IL-8在发疹型药疹、大疱表皮松解型药疹的发病转归中的作用，治疗前血清IL-8含量高于治疗后的血清含量，并且与疾病皮损的面积、严重程度有关。与正常对照组比较，p<0.01，差异有显著性。这证明IL-8在发疹型药疹、大疱表皮松解型药疹的发病中起重要作用。
Medication leads drug eruption by breath in injection and so on. It leads inflammation on skin and mucous, and it may lead death. In recent years, the incidence of EE and TEN, which influences human’s health and qualify of life. Many scholars are studying the mechanism of EE both domestic and abroad. They find that cytokine play an important role during the formation of dermatic inflammation of EE and TEN.
This article study the function TNF-α、IL-8 in the occurrence of EE, both of which is a kind of cytokines household.
Objective:The study uses enzyme linked immunosorbent assay(ELISA) to detect the level of TNF-α and IL-8 in the serum of 26 examples that use the medicine that and didn’t not lead drug eruption.and 30 normal persons and 50 persons with EE and 8 persons With TEN. Group of patients compare with group of contrast. The relativity between the level of TNF-α and IL-8 and skin lesion is analyzed to probe the function of .TNF-αand IL-8 in the occurrence of EE and TEN.
Method:We selected 58 patients with drug eruption who were in-patients in 2nd hospital of JiLin University and Liao Yuan city hospital from May 2001 to November 2003. All patients selected had no treatment of corticosteroid hormone, immunosuppression and antihistamines within 3 weeks. Get blood of vein in morning. And all reserved at -25℃
Result:level of serum TNF-αfor patient group and control group About EE . 5o patient were adopted blood in first week, 32 patients were adopted blood in second week, 15 patients were adopted blood in fourth week, result is that TNF-α’s level of comparing between control group A compared with control group B level of serum TNF-α. Have no a little change. t=0.48 P>0.05 EE. Group patients of first week compare control group A and B. t=15.43、18.69 P<0.01; patients of second week individual compare with control group A and B t=12.76、16.34 P<0.01; patients of fourth week. Compare with control group A t=8.65 P<0.01 , Compare with control group B t=2.91 P>.05; TNE: 8 examples were adopted blood in first week. 8 examples were adopted blood in second week.
5 examples were adopted blood in third week. 5 examples were adopted blood in fourth week. Level of patients in TNF-αfor patients in first week compare with patients in second week. patients in second week compare with patients in third week. Patients third week compare with patients in fourth week.form first week to fourth week is t=4.97、5.33、2.79 there is significant different.
level of serum IL-8 for patient group and control group About EE. result is that IL-8’s level of comparing between control group A compared with control group B level of serum IL-8. Have no a little change. t=0.39 P>0.05 EE. Group patients of first week compare control group A and B. t=22.49、27.91 P<0.01; patients of second week individual compare with control group A and B t=33.16、14.1 P<0.01; patients of fourth week. Compare with control group A t=11.34 P<0.01 , Compare with control group B t=0.41 P>.05; TEN: Level of patients in IL-8 for patients in first week compare with patients in second week. patients in second week compare with patients in third week. Patients third week compare with patients in
fourth week.form first week to fourth week is t=8.79、3.04、2.42 there is significant different.
Discussion: Machanism of DE is complicacy, research proof, the relationship between immunity abnormality and EE and TEN of skin inflammatio’s occurrence、 development becomes more and more concerned TNF-α is monocyte factor, and primarily be produced by monocyte and macropathology; and can increase phagocytosis ability of neutroph.
And increase produce of ,strengthen the ADCC function, and stimulate the cell to take off the grain with, secrete the myeloperoxidase, and cause the cells death, organize to hurt, and strengthen hypersen TNF-α play an important role in system of sitivity cytokine increscent contain. Can cause IL-1, IL-8, IL-6, IFN … etc. change of contain and cause the cytokine for network to lose the balance, and farther mak
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