自从20世纪初发现组胺以来，研究证实其通过与不同细胞表达的4个G蛋白偶联组胺受体结合，对细胞产生重要的病理生理调节作用。
本世纪初，发现组胺H4受体主要在造血细胞表达，而且其具有一定的趋化特性，这些发现让研究人员认为组胺H4受体参与了免疫系统的调节。H4受体调节嗜酸性粒细胞迁移和肥大细胞选择性聚集，导致组胺介导的免疫反应放大，最终引发慢性炎症。H4受体参与了树突状细胞的活化和T细胞的分化，说明其具有一定的免疫调节功能。作为免疫系统组胺受体的一种，H4的特性使得研究者逐渐关注其在炎症性疾病治疗中的作用，如过敏症、哮喘、慢性瘙痒症和自身免疫性疾病。一些研究对人体样本和动物模型中H4受体的配体的有效性进行了探索。然而，在对H4受体的病理生理学功能及治疗作用下定论之前，需要对其相关的作用和药理学上的遗传多态性与种属差异进行深入研究。虽然目前报道的结果存在某些差异，但多数结论认为，组胺诱导的免疫信号中，可将H4受体作为药理学调节的一个靶点，在炎症性疾病的治疗中针对该靶点将会获得较好的结果。
（苏楠 审校）
Zampeli E, et al. Br J Pharmacol. 2009 Mar 20. [Epub ahead of print]
The role of histamine H(4) receptor in immune and inflammatory disorders.
Since its discovery at the beginning of the 20th century, histamine has been established to play a pathophysiological regulatory role in cellular events through binding to four types of G-protein-coupled histamine receptors that are differentially expressed in various cell types. The discovery, at the turn of the millennium, that the histamine H(4) receptor is largely expressed in haemopoietic cells as well as its chemotactic properties designate its regulatory role in the immune system. H(4) receptors modulate eosinophil migration and selective recruitment of mast cells leading to amplification of histamine-mediated immune responses and eventually to chronic inflammation. H(4) receptor involvement in dendritic cell activation and T cell differentiation documents its immunomodulatory function. The characterization of the H(4) as the immune system histamine receptor directed growing attention towards its therapeutic exploitation in inflammatory disorders, such as allergy, asthma, chronic pruritus and autoimmune diseases. The efficacy of a number of H(4) receptor ligands has been evaluated in in vivo and in vitro animal models of disease and in human biological samples. However, before reaching decisive conclusions on H(4) receptor pathophysiological functions and therapeutic exploitation, identification of genetic polymorphisms and interspecies differences in its relative actions and pharmacological profile need to be addressed and taken into consideration. Despite certain variations in the reported findings, the available data strongly point to the H(4) receptor as a novel target for the pharmacological modulation of histamine-transferred immune signals and offer an optimistic perspective for the therapeutic exploitation of this promising new drug target in inflammatory disorders.
