Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases.
Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases.
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DOI：
10.1371/journal.pone.0104479
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mizutani H
中科院分区：
文献类型：
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作者：
Yamanaka K;Nakanishi T;Saito H;Maruyama J;Isoda K;Yokochi A;Imanaka-Yoshida K;Tsuda K;Kakeda M;Okamoto R;Fujita S;Iwakura Y;Suzuki N;Ito M;Maruyama K;Gabazza EC;Yoshida T;Shimaoka M;Mizutani H
皮肤是包含先天免疫系统和获得性免疫系统的免疫器官，因此能够对外源刺激做出反应，产生大量的促炎细胞因子，包括IL-1和IL-1家族成员。表皮IL-1的作用不仅限于启动局部炎症反应，还可以诱导全身炎症。然而，IL-1家族成员在严重皮肤炎症性疾病（如牛皮癣、大疱性表皮松解症、特应性皮炎、起泡性疾病和粘连蛋白-1缺乏综合征）中持续释放与全身性器官疾病的关系迄今尚未得到评估。在这里，我们展示了严重的系统性心血管疾病和代谢异常的发生，包括血管壁异常重塑伴主动脉狭窄、心脏肥大、肢体和尾部循环受损、脂肪组织损失和多器官系统性淀粉样蛋白沉积，并伴有肝肾功能障碍，在皮肤持续释放il -1引起的严重皮炎小鼠模型中。同时给予抗il -1α和IL-1β抗体可改善这些病症。这些发现可以解释动脉硬化、心脏受累、淀粉样变和恶病质在严重全身性皮肤病和全身性自身炎症性疾病中的病态关联，并支持抗il -1治疗全身性炎症性疾病的价值。
The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1α and IL-1β antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases.
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影响因子：
16
作者：
Afonina IS;Tynan GA;Logue SE;Cullen SP;Bots M;Lüthi AU;Reeves EP;McElvaney NG;Medema JP;Lavelle EC;Martin SJ
通讯作者：
Martin SJ
影响因子：
10.8
作者：
Merhi-Soussi, F;Kwak, BR;Gabay, C
通讯作者：
Gabay, C
影响因子：
3
作者：
Nishioka, Tomohiro;Suzuki, Maiko;Imanaka-Yoshida, Kyoko
通讯作者：
Imanaka-Yoshida, Kyoko
影响因子：
13.2
作者：
Fine, JD;Johnson, LB;Suchindran, C
通讯作者：
Suchindran, C
DOI：
10.1038/nri2675
发表时间：
2010-01
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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