ELEVATED TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) BIOLOGICAL-ACTIVITY IN PSORIATIC SKIN-LESIONS
ELEVATED TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) BIOLOGICAL-ACTIVITY IN PSORIATIC SKIN-LESIONS
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DOI：
10.1111/j.1365-2249.1994.tb06244.x
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发表时间：
1994-04-01
影响因子：
4.6
通讯作者：
CAMP, RDR
中科院分区：
文献类型：
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作者：
ETTEHADI, P;GREAVES, MW;CAMP, RDR
银屑病是一种常见的炎症性皮肤病，其病变以表皮增生、白细胞粘附分子表达和白细胞浸润为特征。促炎细胞因子的局部释放，如tnf - α，可能在这些事件的诱导中起重要作用。因此，我们分析了病变和未受累（临床正常）角质层的水提取物中tnf - α免疫反应性和生物活性的存在。肿瘤组织中tnf - α的免疫反应性和生物活性始终高于未受病灶组织。通过使用抗tnf - α中和抗体，证明了测量的生物活性是由于单独存在tnf - α。病变角质层提取物中可溶性TNF受体（p55和p75）的浓度也较高，以p55形式占主导地位。与正常对照相比，银屑病患者血浆中可溶性p55的浓度也有所升高。这些结果证实了免疫反应性TNF- α的存在，并首次最终证明了TNF- α的生物活性和可量化的可溶性TNF受体（p55和p75）浓度在病变银屑病样品中。角质层中tnf - α的恢复可能反映了更深的活性层的合成，在那里它可能发挥其生物效应。可溶性TNF受体的局部和全身释放，特别是p55，可能有助于调节TNF- α在牛皮癣中的作用。
Lesions of the common inflammatory skin disease psoriasis are characterized by epidermal hyperproliferation, leucocyte adhesion molecule expression and leucocyte infiltration. The local release of proinflammatory cytokines, such as TNF-alpha, may play an important role in the induction of these events. We have, therefore, analysed aqueous extracts of lesional and uninvolved (clinically normal) stratum corneum for the presence of TNF-alpha immunoreactivity and biological activity. TNF-alpha immunoreactivity and bioactivity were consistently higher in lesional compared with uninvolved samples. By using an anti-TNF-alpha neutralizing antibody it was demonstrated that the biological activity measured was due to the presence of TNF-alpha alone. Concentrations of soluble TNF receptors (p55 and p75) were also higher in lesional stratum corneum extracts, with the p55 form predominating. The plasma of psoriatic patients was also found to contain elevated concentrations of soluble p55 compared with normal controls. These results confirm the presence of immunoreactive TNF-alpha and, for the first time, conclusively demonstrate TNF-alpha biological activity and quantifiable concentrations of soluble TNF receptors (p55 and p75) in lesional psoriatic samples. TNF-alpha recovery from stratum corneum probably reflects synthesis in deeper, viable layers, where it is likely to exert its biological effects. Local and systemic release of soluble TNF receptors, in particular p55, may serve to regulate the effects of TNF-alpha in psoriasis.