Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany.
Int J Mol Sci. 2021 Jun 6;22(11):6116. doi: 10.3390/ijms22116116.
Histamine is a pleiotropic mediator involved in a broad spectrum of (patho)-physiological processes, one of which is the regulation of inflammation. Compounds acting on three out of the four known histamine receptors are approved for clinical use. These approved compounds comprise histamine H1-receptor (HR) antagonists, which are used to control allergic inflammation, antagonists at HR, which therapeutically decrease gastric acid release, and an antagonist at HR, which is indicated to treat narcolepsy. Ligands at HR are still being tested pre-clinically and in clinical trials of inflammatory diseases, including rheumatoid arthritis, asthma, dermatitis, and psoriasis. These trials, however, documented only moderate beneficial effects of HR ligands so far. Nevertheless, pre-clinically, HR still is subject of ongoing research, analyzing various inflammatory, allergic, and autoimmune diseases. During inflammatory reactions in gut tissues, histamine concentrations rise in affected areas, indicating its possible biological effect. Indeed, in histamine-deficient mice experimentally induced inflammation of the gut is reduced in comparison to that in histamine-competent mice. However, antagonists at HR, HR, and HR do not provide an effect on inflammation, supporting the idea that HR is responsible for the histamine effects. In the present review, we discuss the involvement of histamine and HR in inflammatory and inflammation-associated diseases of the gut.
组胺是一种多效介质，参与广泛的（病理）生理过程，其中之一是炎症的调节。作用于四种已知的组胺受体中的三种的化合物已被批准用于临床。这些已批准的化合物包括组胺 H1 受体（HR）拮抗剂，用于控制过敏炎症；HR 拮抗剂，用于治疗胃酸分泌减少；以及 HR 拮抗剂，用于治疗嗜睡症。HR 的配体仍在进行临床前和炎症性疾病的临床试验中进行测试，包括类风湿性关节炎、哮喘、皮炎和银屑病。然而，这些试验迄今为止仅记录了 HR 配体的适度有益作用。尽管如此，在临床前，HR 仍然是正在进行的研究的主题，分析各种炎症、过敏和自身免疫性疾病。在肠道组织的炎症反应中，受影响区域的组胺浓度升高，表明其可能具有生物学效应。事实上，与组胺功能正常的小鼠相比，在实验诱导的肠道炎症中，缺乏组胺的小鼠的炎症明显减轻。然而，HR、HR 和 HR 的拮抗剂对炎症没有作用，这支持了 HR 负责组胺作用的观点。在本综述中，我们讨论了组胺和 HR 在肠道炎症和炎症相关疾病中的作用。
