Hopkin Sophie J, Lewis Jonathan W, Krautter Franziska, Chimen Myriam, McGettrick Helen M
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom.
Rheumatology Research Group, Arthritis Research UK Centre of Excellence in the Pathogenesis of Rheumatoid Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
Front Pharmacol. 2019 Mar 1;10:184. doi: 10.3389/fphar.2019.00184. eCollection 2019.
Leukocyte recruitment is a pivotal process in the regulation and resolution of an inflammatory episode. It is vital for the protective responses to microbial infection and tissue damage, but is the unwanted reaction contributing to pathology in many immune mediated inflammatory diseases (IMIDs). Indeed, it is now recognized that patients with IMIDs have defects in at least one, if not multiple, check-points regulating the entry and exit of leukocytes from the inflamed site. In this review, we will explore our understanding of the imbalance in recruitment that permits the accumulation and persistence of leukocytes in IMIDs. We will highlight old and novel pharmacological tools targeting these processes in an attempt to trigger resolution of the inflammatory response. In this context, we will focus on cytokines, chemokines, known pro-resolving lipid mediators and potential novel lipids (e.g., sphingosine-1-phosphate), along with the actions of glucocorticoids mediated by 11-beta hydroxysteroid dehydrogenase 1 and 2.
白细胞募集是炎症反应调节和消退过程中的关键环节。它对于抵御微生物感染和组织损伤的保护性反应至关重要，但在许多免疫介导的炎症性疾病（IMIDs）中却是导致病理变化的不良反应。事实上，现在人们认识到，IMIDs患者在调节白细胞进出炎症部位的至少一个（如果不是多个）检查点存在缺陷。在这篇综述中，我们将探讨对募集失衡的理解，这种失衡使得白细胞在IMIDs中得以积累和持续存在。我们将重点介绍针对这些过程的传统和新型药理学工具，试图引发炎症反应的消退。在此背景下，我们将关注细胞因子、趋化因子、已知的促消退脂质介质和潜在的新型脂质（如鞘氨醇-1-磷酸），以及由11-β羟类固醇脱氢酶1和2介导的糖皮质激素的作用。
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