Ako Research Institute, Otsuka Pharmaceutical Co., Ltd, Hyogo, Japan; Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Ako Research Institute, Otsuka Pharmaceutical Co., Ltd, Hyogo, Japan.
J Invest Dermatol. 2014 Jun;134(6):1561-1569. doi: 10.1038/jid.2014.31. Epub 2014 Jan 21.
Psychological factors have long been assumed to be involved in the pathogenesis of allergic skin diseases. The effects of psychological stress on allergic contact dermatitis (ACD) have been experimentally well investigated; however, the effects of ACD on stress responses are largely unknown. Here, we report that preceding chronic ACD dramatically affects the behavioral and physiological stress responses to social isolation (a psychological stressor). In male BALB/c mice, social isolation combined with long-standing (>2 months) ACD by repeated hapten application caused characteristic symptoms, including chronic dermatitis from persistent self-scratching, behavioral changes related to fear/anxiety, and elevated serum IgE levels. The symptoms were maintained by social isolation alone without further hapten application after the onset, and were improved by resocialization. Treatment with topical corticosteroids exacerbated chronic scratch dermatitis, whereas it was effective for chronic ACD. These results show that the symptoms represent a de novo development of a specific disease state and not a mere exacerbation of a preexisting allergic inflammation. With this experimental protocol, similar results were obtained in several other strains of mice. This murine model provides a tool for investigating the pathogenesis and treatment of allergic skin disease with psychodermatological aspects.
心理因素长期以来一直被认为与过敏性皮肤疾病的发病机制有关。心理应激对过敏性接触性皮炎(ACD)的影响已得到充分的实验研究;然而,ACD 对应激反应的影响在很大程度上尚不清楚。在这里,我们报告称,慢性 ACD 会显著影响对社会隔离(一种心理应激源)的行为和生理应激反应。在雄性 BALB/c 小鼠中,社会隔离与通过重复应用变应原引起的长期(>2 个月)ACD 相结合,导致了包括持续性自我搔抓引起的慢性皮炎、与恐惧/焦虑相关的行为改变以及血清 IgE 水平升高在内的特征性症状。在发病后,仅通过社会隔离即可维持这些症状,而无需进一步的变应原应用,重新社交化则可改善这些症状。局部皮质类固醇治疗会加重慢性搔抓性皮炎,而对慢性 ACD 则有效。这些结果表明,这些症状代表了一种新的特定疾病状态的发展,而不是预先存在的过敏炎症的单纯恶化。使用这种实验方案,在其他几种小鼠品系中也获得了类似的结果。这种小鼠模型为研究具有精神皮肤病学方面的过敏性皮肤疾病的发病机制和治疗提供了一种工具。