Swinkels O Q J, Prins M, Gerritsen M J P, van Vlijmen-Willems I M J J, van der Valk P G M, van de Kerkhof P C M
Department of Dermatology, University Medical Centre Nijmegen, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands.
Skin Pharmacol Appl Skin Physiol. 2002 Nov-Dec;15(6):393-400. doi: 10.1159/000066450.
Dithranol, although a time-honoured treatment and from the beginning of the previous century still going strong, remains an empirical treatment. There is growing evidence that the biochemical basis for the mechanism of action of dithranol at the molecular level is related to the redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical and hydroxyl radical. Some authors suggest that epidermal proliferation and/or keratinisation may be the target for dithranol, while others refer to aspects of cutaneous inflammation as crucial in the antipsoriatic effect of dithranol. The present study aims to analyse the effect of single and repeated applications of dithranol on aspects of epidermal proliferation, keratinisation and inflammation in the psoriatic plaque. The most marked effect of dithranol proved to be that on epidermal proliferation (the number of Ki-67-positive nuclei) with an early reduction already 1 day following the single application. This reduction lasted for 16 days. However, such an application induced only a modest clinical improvement. Repeated challenges, resulting in a decrease in the number of Ki-67-positive nuclei of 66%, led to a substantial clinical improvement after 12 days. Repeated challenges resulted in a significant reduction of the number of polymorphonuclear leucocytes. However, this reduction was less pronounced as compared to the effect on epidermal proliferation. It is concluded that epidermal proliferation is a sensitive marker to demonstrate an early effect of dithranol. The dynamics of the cell-biological responses suggest that intermittent applications might be a promising new approach. As dithranol does not reduce the number of T lymphocytes, it is attractive to speculate that the combination of dithranol with immunosuppressive treatments might be a very effective combination.
地蒽酚虽是一种历史悠久的疗法，自上世纪初沿用至今且仍广泛应用，但它仍是一种经验性治疗方法。越来越多的证据表明，地蒽酚在分子水平上的作用机制的生化基础与氧化还原活性有关，氧化还原活性会导致活性氧的产生，其中包括单线态氧、超氧阴离子自由基和羟基自由基。一些作者认为表皮增殖和/或角质化可能是地蒽酚的作用靶点，而另一些人则指出皮肤炎症方面在其治疗银屑病的效果中起关键作用。本研究旨在分析单次和重复应用地蒽酚对银屑病斑块中表皮增殖、角质化和炎症方面的影响。结果证明，地蒽酚对表皮增殖（Ki-67阳性细胞核数量）的影响最为显著，单次应用后1天就出现早期减少。这种减少持续了16天。然而，这样的应用仅带来了适度的临床改善。重复给药导致Ki-67阳性细胞核数量减少66%，12天后带来了显著的临床改善。重复给药导致多形核白细胞数量显著减少。然而，与对表皮增殖的影响相比，这种减少不太明显。结论是表皮增殖是证明地蒽酚早期效果的敏感标志物。细胞生物学反应的动态变化表明，间歇性应用可能是一种有前景的新方法。由于地蒽酚不会减少T淋巴细胞数量，推测地蒽酚与免疫抑制治疗联合可能是一种非常有效的组合很有吸引力。
