Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London, UK.
Comparative Biological Sciences, Royal Veterinary College, University of London, London, UK.
Br J Pharmacol. 2019 Apr;176(8):1009-1023. doi: 10.1111/bph.14587. Epub 2019 Mar 1.
We are all too familiar with the events that follow a bee sting-heat, redness, swelling, and pain. These are Celsus' four cardinal signs of inflammation that are driven by very well-defined signals and hormones. In fact, targeting the factors that drive this onset phase is the basis upon which most current anti-inflammatory therapies were developed. We are also very well aware that within a few hours, these cardinal signs normally disappear. In other words, inflammation resolves. When it does not, inflammation persists, resulting in damaging chronic conditions. While inflammatory onset is actively driven, so also is its resolution-years of research have identified novel internal counter-regulatory signals that work together to switch off inflammation. Among these signals, lipids are potent signalling molecules that regulate an array of immune responses including vascular hyper reactivity and pain, as well as leukocyte trafficking and clearance, so-called resolution. Here, we collate bioactive lipid research to date and summarize the major pathways involved in their biosynthesis and their role in inflammation, as well as resolution. LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
我们对被蜜蜂蜇后的一系列反应再熟悉不过了——发热、红肿、肿胀和疼痛。这是塞勒斯（Celsus）描述的炎症的四大主要特征，这些特征由非常明确的信号和激素驱动。事实上，针对驱动这一发作阶段的因素，是大多数当前抗炎疗法的基础。我们也非常清楚，在几个小时内，这些主要特征通常会消失。换句话说，炎症会消退。如果没有，炎症就会持续，导致慢性损害。炎症发作是积极驱动的，其消退也是如此——多年的研究已经确定了新的内在的抗炎症信号，这些信号协同作用来关闭炎症。在这些信号中，脂质是有效的信号分子，可调节包括血管高反应性和疼痛、白细胞迁移和清除等一系列免疫反应，即所谓的炎症消退。在这里，我们整理了迄今为止有关生物活性脂质的研究，并总结了它们在生物合成中的主要途径及其在炎症和消退中的作用。相关文章：本文是 1982 年诺贝尔奖 35 周年纪念主题部分关于类二十烷酸的文章之一：我们现在在哪里？要查看本部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
