Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura 248-8555, Kanagawa, Japan.
Toray Industries, Inc., Pharmaceutical Research Laboratories, 10-1, Tebiro 6-chome, Kamakura 248-8555, Kanagawa, Japan.
Eur J Pharmacol. 2018 Jun 5;828:26-30. doi: 10.1016/j.ejphar.2018.03.018. Epub 2018 Mar 12.
Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system, especially activation of IL-23/IL-17 axis, has been strongly implicated in the pathogenesis of psoriasis. For example, anti-IL-23 therapy is effective in psoriasis patients, and thus IL-23 is considered as a potential therapeutic target for the treatment of psoriasis. The skin barrier provides protection of the human body against infection from external pathogens. Dysfunction of the skin barrier is also one of the characteristics in psoriasis and is correlated with disease severity. However, there have been no reports regarding the effectiveness of antipsoriatic agents on the skin barrier dysfunction of psoriasis. In this study, we examined the effect of anti-IL-12/IL-23p40 monoclonal antibody (p40 mAb) on dermatitis symptoms and skin barrier dysfunction in mice with imiquimod-induced psoriasis-like dermatitis. We found that p40 mAb suppressed epidermal thickness and increased transepidermal water loss (TEWL) as indicator for skin barrier function with accompanying suppression of IL-23p19, IL-17A, IL-22, and keratin 16 gene expression. These results suggest that p40 mAb is not only effective against dermatitis symptoms but also skin barrier dysfunction in mice with imiquimod-induced psoriasis-like dermatitis. This is the first report on the effect of p40 mAb on skin barrier dysfunction related to psoriasis. Taken together, our results indicate the possibility of new insights as well as the therapeutic potential of anti-IL-23 for the treatment of psoriasis.
银屑病是一种慢性炎症性皮肤病，其特征为红斑、皮肤增生、鳞屑和角质形成细胞过度增殖。虽然银屑病的确切病因尚不清楚，但失调的免疫系统，特别是 IL-23/IL-17 轴的激活，强烈提示与银屑病的发病机制有关。例如，抗 IL-23 治疗对银屑病患者有效，因此 IL-23 被认为是治疗银屑病的潜在治疗靶点。皮肤屏障为人体提供了抵御外部病原体感染的保护。皮肤屏障功能障碍也是银屑病的特征之一，与疾病严重程度相关。然而，目前尚无关于抗银屑病药物对银屑病皮肤屏障功能障碍的疗效的报道。在这项研究中，我们研究了抗 IL-12/IL-23p40 单克隆抗体（p40 mAb）对咪喹莫特诱导的银屑病样皮炎小鼠的皮炎症状和皮肤屏障功能障碍的影响。我们发现，p40 mAb 抑制表皮厚度增加和经表皮水分流失（TEWL），作为皮肤屏障功能的指标，同时伴有 IL-23p19、IL-17A、IL-22 和角蛋白 16 基因表达的抑制。这些结果表明，p40 mAb 不仅对皮炎症状有效，而且对咪喹莫特诱导的银屑病样皮炎小鼠的皮肤屏障功能障碍也有效。这是关于 p40 mAb 对与银屑病相关的皮肤屏障功能障碍影响的首次报道。综上所述，我们的研究结果为抗 IL-23 治疗银屑病提供了新的见解和治疗潜力。
