Hsia Edward, Johnston Michael J, Houlden Robert J, Chern Wendy H, Hofland Hans E J
Center for Skin Biology, Stiefel Laboratories Inc., Palo Alto, California 94304, USA.
J Invest Dermatol. 2008 Jan;128(1):125-30. doi: 10.1038/sj.jid.5700968. Epub 2007 Jul 19.
Oral acitretin is currently indicated for the treatment of severe psoriasis in adults, but its use is limited by systemic side effects and teratogenicity. Topical administration of acitretin may lessen the risk of systemic toxicity while increasing local bioavailability in the skin. The effects of topical acitretin on reconstructed human epidermis (RHE) and Rhino mice were investigated and compared to those of currently marketed topical retinoids: tretinoin and tazarotene. In acitretin-treated RHE cultures, there was a reduction in keratohyalin granules and filaggrin expression in the stratum granulosum, a loss of keratin 10 expression in the stratum spinosum, and an increase in keratin 19 expression in all viable cell layers. All retinoids showed similar signs of activity in RHE cultures. Furthermore, the release of pro-inflammatory cytokines IL-1alpha and IL-8 in RHE cultures was less pronounced with acitretin compared to tretinoin- and tazarotene-containing formulations, suggesting that acitretin may be less irritating. In Rhino mice, acitretin induced a local, dose-dependent reduction in utricle diameter after seven daily dermal doses. A similar effect was observed in tretinoin- and tazarotene-treated mice. Our data suggest that topical application of acitretin may have a therapeutic benefit in the local management of keratinization disorders.
阿维A目前被用于治疗成人重度银屑病，但其使用受到全身副作用和致畸性的限制。局部应用阿维A可能会降低全身毒性风险，同时增加皮肤局部的生物利用度。研究了局部应用阿维A对重建人表皮（RHE）和Rhino小鼠的影响，并与目前市售的局部维甲酸类药物：维甲酸和他扎罗汀进行比较。在阿维A处理的RHE培养物中，颗粒层中透明角质颗粒和丝聚蛋白表达减少，棘层中角蛋白10表达缺失，所有存活细胞层中角蛋白19表达增加。所有维甲酸类药物在RHE培养物中均表现出相似的活性迹象。此外，与含维甲酸和他扎罗汀的制剂相比，阿维A处理的RHE培养物中促炎细胞因子IL-1α和IL-8的释放不那么明显，这表明阿维A的刺激性可能较小。在Rhino小鼠中，连续7天每日经皮给药后，阿维A诱导毛囊直径出现局部剂量依赖性减小。在维甲酸和他扎罗汀处理的小鼠中也观察到类似效果。我们的数据表明，局部应用阿维A可能对角化异常的局部治疗有益。
