Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Invest Dermatol. 2019 Jun;139(6):1329-1338.e7. doi: 10.1016/j.jid.2019.01.029. Epub 2019 Feb 15.
Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself is correlated with hyperglycemia in humans and mice. In patients, the severity of psoriasis was correlated with high blood glucose levels, and treatment of psoriasis by phototherapy improved insulin secretion. Imiquimod-induced systemic and cutaneous inflammation in mice, with features of human psoriasis, also resulted in hyperglycemia. Although it should be determined if psoriasis-like cutaneous inflammation alone can induce hyperglycemia, imiquimod-treated mice showed impairment of insulin secretion without significant islet inflammation. Administration of anti-IL-17A monoclonal antibody improved hyperglycemia in patients with psoriasis and imiquimod-treated mice with psoriasiform features. These results suggest that hyperglycemia is highly associated with psoriasis, mainly through IL-17.
慢性低度炎症可引起多种代谢综合征。患有银屑病(一种慢性免疫性皮肤炎症)的患者常发生糖尿病。然而,目前尚不清楚银屑病如何导致或与葡萄糖耐量不良相关。在这里,我们研究了银屑病本身是否与人类和小鼠的高血糖相关。在患者中,银屑病的严重程度与高血糖水平相关,光疗治疗银屑病可改善胰岛素分泌。咪喹莫特诱导的全身性和皮肤炎症在小鼠中,具有人类银屑病的特征,也导致高血糖。虽然应该确定是否仅银屑病样皮肤炎症就能诱导高血糖,但咪喹莫特治疗的小鼠表现出胰岛素分泌受损而胰岛炎症不明显。给予抗 IL-17A 单克隆抗体可改善银屑病患者和具有银屑病样特征的咪喹莫特治疗小鼠的高血糖。这些结果表明,高血糖与银屑病密切相关,主要通过 IL-17。