个体定制抗炎症治疗新进展

一项研究发现，人们对阿司匹林的反应各异可能为炎症和痊愈的个体差异提供了线索。

Derek Gilroy及其同事使用除疣贴让人类志愿者的前臂出现了水泡，然后评估了受试者的痊愈过程。这组作者发现，此前对低剂量的阿司匹林显示抗炎症应答的人表现出了在72小时内水疱的生长和痊愈，而那些免疫系统对阿司匹林没有反应的人出现了痊愈更慢的水疱。已知阿司匹林能够促进称为脂氧素 ( lipoxins) 的炎症控制分子的制造。

该研究发现，水疱痊愈更快的人比水疱在72小时内没有痊愈的人的脂氧素基准浓度更低。这组作者提出，发出开始痊愈的指示可能在天然产生高量脂氧素的人的体内饱和，而脂氧素浓度低的人们的免疫系统可能受到阿司匹林或外伤引发的炎症的刺激，从而表现出更迅速的炎症消退和痊愈。

这组作者说，这项研究可能帮助科学家根据个体免疫应答从而为患者定制抗炎症治疗。

点击此处下载原文

Dichotomy in duration and severity of acute inflammatory responses in humans
arising from differentially expressed proresolution pathways
Thea Morris¹, Melanie Stables¹, Paul Colville-Nash², Justine Newson¹, Geoffrey Bellingan³, Patricia M. de Souza⁴, and Derek W. Gilroy¹

1.Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1E 6JJ, United Kingdom;
2.South West Thames Institute for Renal Research, St. Helier Hospital, Carshalton SM5 1AA, United Kingdom;
3.Critical Care, University College London Hospitals National Health Service Foundation Trust, London NW1 2BU, United Kingdom;
4.Cardiothoracic Pharmacology Department, Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom

【Abstract】Lipoxins (Lxs) and aspirin-triggered epi-Lxs (15-epi-LxA4) act through the ALX/FPRL1 receptor to block leukocyte trafficking, dampen cytokine/chemokine synthesis, and enhance phagocytic clearance of apoptotic leukocytes—key requisites for inflammatory resolution. Although studies using primarily inbred rodents have highlighted resolution as an active event, little is known about the role resolution pathways play in controlling the duration/profile of inflammatory responses in humans. To examine this, we found two types of responders to cantharidin-induced skin blisters in male healthy volunteers: those with immediate leukocyte accumulation and cytokine/chemokine synthesis followed by early resolution and a second group whose inflammation increased gradually over time followed by delayed resolution. In early resolvers, blister 15-epi-LxA4 and leukocyte ALX were low, but increased as inflammation abated. In contrast, in delayed resolvers, 15-epi-LxA4 and ALX were high early in the response but waned as inflammation progressed. Elevating 15-epi-LxA4 in early resolvers using aspirin increased blister leukocyte ALX but reduced cytokines/chemokines as well as polymorphonuclear leukocyte and macrophage numbers. These findings show that two phenotypes exist in humans with respect to inflammation severity/longevity controlled by proresolution mediators, namely 15-epi-LxA4. These data have implications for understanding the etiology of chronic inflammation and future directions in antiinflammatory therapy.