Alvarez Pilar, Jensen Liselotte E
Department of Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, 1158 MERB, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Mediators Inflamm. 2016;2016:6756138. doi: 10.1155/2016/6756138. Epub 2016 Dec 12.
Generalized pustular psoriasis (GPP) is a severe form of psoriasis that can be caused by missense mutations in the interleukin-36 (IL-36) receptor antagonist. In addition to neutrophil rich skin inflammation, GPP patients typically also experience anorexia, fever, malaise, and pain. The imiquimod-induced skin inflammation mouse model has rapidly become a popular way to study plaque psoriasis, which typically does not involve symptoms of systemic disease. In this model, neutrophil recruitment to the skin is dependent upon the inflammatory mediators IL-1, via its receptor IL-1R1, and IL-36. Unexpectedly, we observed that mice also exhibited signs of anorexia (weight loss and decreased food intake), general malaise (decreased activity and loss of interest in building nests), and pain (nose bulging and hunched posture). A scoring system allowing quantitative comparisons of test groups was developed. Female mice were found to develop more severe disease than male mice. Furthermore, mice deficient in both IL-1R1 and IL-36 are nearly disease-free, while mice lacking only one of these inflammatory mediators have less severe disease than wild type mice. Hence, the imiquimod-induced skin inflammation mouse model recapitulates not only plaque psoriasis, but also the more severe symptoms, that is, anorexia, malaise, and pain, seen in GPP.
泛发性脓疱型银屑病（GPP）是银屑病的一种严重形式，可由白细胞介素-36（IL-36）受体拮抗剂中的错义突变引起。除了富含中性粒细胞的皮肤炎症外，GPP患者通常还会出现厌食、发热、不适和疼痛。咪喹莫特诱导的皮肤炎症小鼠模型已迅速成为研究斑块状银屑病的常用方法，斑块状银屑病通常不涉及全身性疾病症状。在该模型中，中性粒细胞向皮肤的募集依赖于炎症介质IL-1，通过其受体IL-1R1，以及IL-36。出乎意料的是，我们观察到小鼠还表现出厌食迹象（体重减轻和食物摄入量减少）、全身不适（活动减少和筑巢兴趣丧失）和疼痛（鼻子鼓起和弓背姿势）。开发了一种评分系统，用于对测试组进行定量比较。发现雌性小鼠比雄性小鼠患更严重的疾病。此外，IL-1R1和IL-36均缺陷的小鼠几乎无病，而仅缺乏这些炎症介质之一的小鼠比野生型小鼠的疾病严重程度更低。因此，咪喹莫特诱导的皮肤炎症小鼠模型不仅重现了斑块状银屑病，还重现了GPP中出现的更严重症状，即厌食、不适和疼痛。
