Serhan Charles N
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
FASEB J. 2017 Apr;31(4):1273-1288. doi: 10.1096/fj.201601222R. Epub 2017 Jan 13.
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered pathophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (, arthritis and periodontal diseases). The inflammatory response, when self-limited, produces a superfamily of chemical mediators that stimulate resolution of the response. Specialized proresolving mediators (SPMs), identified in recent years, are endogenous mediators that include the n-3-derived families resolvins, protectins, and maresins, as well as arachidonic acid-derived (n-6) lipoxins, which promote resolution of inflammation, clearance of microbes, reduction of pain, and promotion of tissue regeneration novel mechanisms. Aspirin and statins have a positive impact on these resolution pathways, producing epimeric forms of specific SPMs, whereas other drugs can disrupt timely resolution. In this article, evidence from recent human and preclinical animal studies is reviewed, indicating that SPMs are physiologic mediators and pharmacologic agonists that stimulate resolution of inflammation and infection. The findings suggest that it is time to challenge current treatment practices-namely, using inhibitors and antagonists alone-and to develop immunoresolvents as agonists to test resolution pharmacology and their role in catabasis for their therapeutic potential.-Serhan, C. N. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms.
从希波克拉底时代及更早时期起，古代社会的行医者就认识到炎症的迹象，如发热、发红、肿胀和疼痛，并使用能阻断或抑制促炎化学介质的药物进行治疗。如今有了更具选择性的药物，但这一治疗理念并未改变。由于急性炎症反应对宿主具有保护作用，可遏制外来入侵者，当今药典中的许多药物会导致严重的不良副作用，如免疫抑制。现在，不受控制的炎症被认为是病理生理状态，并与许多广泛发生的疾病相关，如心血管疾病、神经退行性疾病、糖尿病、肥胖症和哮喘，以及经典的炎症性疾病（如关节炎和牙周疾病）。当炎症反应自我限制时，会产生一类化学介质超家族，刺激炎症反应的消退。近年来发现的专门促消退介质（SPMs）是内源性介质，包括n-3衍生的消退素、保护素和maresins家族，以及花生四烯酸衍生的（n-6）脂氧素，它们可促进炎症消退、清除微生物、减轻疼痛并促进组织再生 新机制。阿司匹林和他汀类药物对这些消退途径有积极影响，可产生特定SPMs的差向异构体形式，而其他药物可能会干扰及时的消退过程。在本文中，我们回顾了近期人体和临床前动物研究的证据，表明SPMs是刺激炎症和感染消退的生理介质和药理激动剂。这些发现表明，是时候挑战当前的治疗方法了——即仅使用抑制剂和拮抗剂——并开发免疫消退剂作为激动剂，以测试消退药理学及其在疾病转归中的作用以及它们的治疗潜力。——塞尔汗，C. N. 21世纪治疗炎症和感染：从解析消退介质和机制中获得的新线索。
