Lange R W, Hayden P J, Chignell C F, Luster M I
Environmental Immunology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. lange+@pitt.edu
Inflamm Res. 1998 Apr;47(4):174-81. doi: 10.1007/s000110050313.
Topical application of anthralin, used in the treatment of psoriasis, is often accompanied by severe skin inflammation, presumably due to free radical products of the drug. The role of inflammatory cytokines and their induction by anthralin-derived reactive oxygen species were studied in cultures of normal human keratinocytes (NHKs).
Anthralin was added to cultures of NHKs in the presence or absence of various antioxidants, including superoxide dismutase, tetramethylthiourea, N-acetylcysteine and vitamin E and relative changes in cytokine secretion and in the number of mRNA transcripts were examined. In addition, NHKs were either treated with neutralizing antibodies to tumor necrosis factor (TNF)-alpha or transfected with a CAT-linked IL-8 promoter to establish the direct effects of anthralin on chemokine synthesis.
Anthralin, at concentrations between 5 microM and 25 microM, caused a marked increase in granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-6, IL-8 and TNFalpha synthesis that was selectively inhibited by specific antioxidants. Furthermore, anthralin induced chemokine secretion without the need of primary cytokines.
Taken together, these studies suggest that oxygen radicals generated from anthralin are responsible for the induction of inflammatory cytokines which, in turn contributes to their dermal toxicity.
用于治疗银屑病的蒽林局部应用时，常伴有严重的皮肤炎症，推测这是由于该药物的自由基产物所致。在正常人角质形成细胞（NHK）培养物中研究了炎性细胞因子的作用及其由蒽林衍生的活性氧诱导的情况。
在存在或不存在各种抗氧化剂（包括超氧化物歧化酶、四甲基硫脲、N - 乙酰半胱氨酸和维生素E）的情况下，将蒽林添加到NHK培养物中，并检测细胞因子分泌和mRNA转录本数量的相对变化。此外，用肿瘤坏死因子（TNF）-α中和抗体处理NHK或用与氯霉素乙酰转移酶（CAT）相连的白细胞介素 - 8（IL - 8）启动子转染NHK，以确定蒽林对趋化因子合成的直接影响。
浓度在5微摩尔至25微摩尔之间的蒽林导致粒细胞巨噬细胞集落刺激因子（GM - CSF）、白细胞介素（IL）-6、IL - 8和TNFα的合成显著增加，而特定抗氧化剂可选择性抑制这种增加。此外，蒽林无需初级细胞因子即可诱导趋化因子分泌。
综上所述，这些研究表明蒽林产生的氧自由基是诱导炎性细胞因子的原因，进而导致其皮肤毒性。
