Victor Frank C, Gottlieb Alice B
UMDNJ/RWJMS-Clinical Research Center, 51 French Street, P.O. Box 19, Acute Care Bldg. 3rd Floor, New Brunswick, New Jersey 08901-0019, USA.
J Drugs Dermatol. 2002 Dec;1(3):264-75.
TNF-alpha is a key cytokine in innate immune responses and is increased in psoriatic lesions. TNF-alpha has many effects, ranging from inflammation to apoptosis. These effects are reviewed to better understand the role of TNF-alpha as it relates to the pathogenesis and treatment of psoriasis. TNF-alpha increases production of pro-inflammatory molecules (e.g. IL-1, IL-6, IL-8, NF-kappa B, vasoactive intestinal peptide) and adhesion molecules (e.g. intercellular adhesion molecule-1, P-selectin, E-selectin). TNF-alpha promotes apoptosis through binding to the TNF-receptor 1; however, psoriatic lesions are hyperproliferative despite an increase in TNF-alpha. This paradox is partially explained as NF-kappa B activation seems to inhibit TNF-alpha-induced apoptosis. The importance of TNF-alpha and apoptosis in psoriasis is shown through the review of clinical trials using anti-TNF-alpha immunobiologics (e.g. etanercept, infliximab) and apoptosis-inducing treatments that result in clinical improvement of the disease.
肿瘤坏死因子-α（TNF-α）是先天性免疫反应中的关键细胞因子，在银屑病皮损中含量升高。TNF-α具有多种作用，从炎症到细胞凋亡。对这些作用进行综述，以更好地理解TNF-α在银屑病发病机制和治疗中所起的作用。TNF-α可增加促炎分子（如白细胞介素-1、白细胞介素-6、白细胞介素-8、核因子-κB、血管活性肠肽）和黏附分子（如细胞间黏附分子-1、P-选择素、E-选择素）的产生。TNF-α通过与TNF受体1结合促进细胞凋亡；然而，尽管TNF-α含量增加，银屑病皮损仍呈过度增殖状态。这种矛盾现象部分可解释为核因子-κB的激活似乎抑制了TNF-α诱导的细胞凋亡。通过回顾使用抗TNF-α免疫生物制剂（如依那西普、英夫利昔单抗）以及诱导细胞凋亡治疗的临床试验，这些治疗可使疾病临床症状改善，从而表明了TNF-α和细胞凋亡在银屑病中的重要性。
