Ulloa Luis
Center of Immunology and Inflammation, Institute for Medical Research, North Shore University Hospital, 350 Community Drive, New York 11030, USA.
Nat Rev Drug Discov. 2005 Aug;4(8):673-84. doi: 10.1038/nrd1797.
Physiological anti-inflammatory mechanisms are selected by evolution to effectively control the immune system and can be exploited for the treatment of inflammatory disorders. Recent studies indicate that the vagus nerve (which is the longest of the cranial nerves and innervates most of the peripheral organs) can modulate the immune response and control inflammation through a 'nicotinic anti-inflammatory pathway' dependent on the alpha7-nicotinic acetylcholine receptor (alpha7nAChR). Nicotine has been used in clinical trials for the treatment of ulcerative colitis, but its clinical applications are limited by its unspecific effects and subsequent toxicity. This article reviews recent advances supporting the therapeutic potential of selective nicotinic agonists in several diseases. Similar to the development of alpha- and beta-agonists for adrenoceptors, selective agonists for alpha7nAChR could represent a promising pharmacological strategy against infectious and inflammatory diseases.
生理抗炎机制是进化选择出来用以有效控制免疫系统的，可用于治疗炎症性疾病。最近的研究表明，迷走神经（它是最长的脑神经，支配大部分外周器官）可通过依赖α7-烟碱型乙酰胆碱受体（α7nAChR）的“烟碱抗炎途径”调节免疫反应并控制炎症。尼古丁已用于治疗溃疡性结肠炎的临床试验，但其临床应用因非特异性作用及后续毒性而受到限制。本文综述了支持选择性烟碱激动剂在几种疾病中治疗潜力的最新进展。类似于肾上腺素能受体α和β激动剂的研发，α7nAChR的选择性激动剂可能代表一种针对感染性和炎症性疾病的有前景的药理学策略。
