Focus on the role of substance P in chronic urticaria

BACKGROUND: Emerging data have strengthened the importance of substance P (SP) as a proinflammatory mediator in human pathology. A role for SP in the pathogenesis of urticaria has long been hypothesized. METHODS: Literature data regarding the possible role of SP in chronic urticaria/chronic spontaneous urticaria (CSU) have been reviewed and summarized in this manuscript. This review is based on pertinent articles that were retrieved by a selective literature search in the PubMed database. Articles in English published up to July 2018 were taken into consideration. RESULTS: Recent studies in patients with CSU have demonstrated that circulating levels of SP are significantly elevated, in correlation with disease severity, and that SP-positive basophils are upregulated. SP has been shown to trigger degranulation in basophils derived from CSU patients. Moreover, SP can be involved in pseudoallergic reactions and may act as a histamine-releasing factor in a subset of patients with CSU. Current evidence suggests that the biological activity of SP can be exerted not only through the conventional NK-1 receptor but also through the recently identified Mas-related G protein-coupled receptors. MRGPRX2 can cause mast cell activation and has been found to be upregulated in the skin of patients with severe chronic urticaria. CONCLUSIONS: Many findings seem to support the pathogenic involvement of SP in chronic urticaria/CSU. However, further studies are necessary to elucidate the role of SP as a mediator in CSU pathogenesis and a potential new therapeutic target.