Effects of Rupatadine on Platelet- Activating Factor–Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

Abstract

Background: Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine. Methods: The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs. Results: CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not. Conclusions: This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.

The clinical evidence of second-generation H1-antihistamines in the treatment of allergic rhinitis and urticaria in children over 2 years with a special focus on rupatadine

“…Some ethical issues are related to children's vulnerability, informed consent, and confidentiality, while methodological issues are related to the heterogeneous nature of childhood itself according to different ages. Therefore, only few clinical studies on sgAH have been performed in children based on current guidelines using validated assessment tools for allergic rhinitis and urticaria [11][12][13][14][15][16][17][19][20][21][22][23][24][25]. As a consequence, an additional ethical problem arises: children (the younger the more) are who do not or later benefit from the medical progress.…”

“…In allergic rhinitis, these reactions are associated with increased vascular permeability, eosinophil chemoattraction, and airway hyperresponsiveness. Increased plasma levels of PAF have been reported in patients with urticaria compared with healthy controls [12][13][14][15][16][17]. Additionally, recent findings in CSU patients, particularly those with sgAH refractoriness, showed significant increases in serum PAF levels and decreases in PAF-AH.…”

Management of dengue infection: improving morbidity

“…Plateletactivating factor (PAF) is a lipid mediator released by mast cells and eosinophils in humans. Its action in the development of allergic diseases is well known [41]. It had been noted that PAF is elevated during acute dengue infection and may be an important mediator in plasma leak.…”

“…Rupatadine, an H1 receptor antagonist is used for the treatment of allergic conditions. Rupatadine has been identified to have an inhibitory action on PAF receptors as well [41]. Therefore rupatadine might modulate dengue-associated vascular leak acting through PAF receptors.…”

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

“…PAF has been implicated in other allergic disorders, such as anaphylaxis and allergic rhinitis. Although the relevance of PAF is well established in the pathophysiology of these diseases, there has been limited research exploring the role that PAFr antagonists might play in treating these diseases . Given the increasing incidence of allergic disorders, further studies are required in this area …”