Platelet-Activating Factor (PAF) in Allergic Rhinitis: Clinical and Therapeutic Implications

Abstract

Platelet-activating factor (PAF) is a lipid mediator involved in several allergic reactions. It is released from multiple cells of the immune system, such as eosinophils, neutrophils, and mast cells, and also exerts its effect on most of them upon specific binding to its receptor, becoming a pleiotropic mediator. PAF is considered a potential relevant mediator in allergic rhinitis, with a key role in nasal congestion and rhinorrhoea due to its effect on vascular permeability. Interestingly, despite its potential relevance as a therapeutic target, no specific PAF inhibitors have been studied in humans. However, rupatadine, a second-generation antihistamine with dual antihistamine and anti-PAF effects has shown promising results by both blocking nasal symptoms and inhibiting mast cell activation induced by PAF, in comparison to antihistamine receptor drugs. In conclusion, the inhibition of PAF may be an interesting approach in the treatment of allergic rhinitis as part of a global strategy directed at blocking as many relevant inflammatory mediators as possible.

HDAC inhibitor sodium butyrate prevents allergic rhinitis and alters lncRNA and mRNA expression profiles in the nasal mucosa of mice

“…In the top 10 significantly enriched GO terms in NaB + AR vs. AR groups, salmon cartilage proteoglycan attenuates allergic responses in mice (55). Inhibiting platelet activating factor can treat AR (56). Among top 10 significantly enriched GO terms in NaB+AR vs. c groups, immunoglobulin E (lgε) receptor on lymphocyte γ chain can mediate the receptor activator for NF-κB ligand, which is the primary cytokine required for osteoclastogenesis (57).…”

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.…”

“…One of these guidelines is ARIA (Allergic Rhinitis and its Impact on Asthma), which consider that appropriate treatment of AR may improve patients' QoL, learning, and work productivity. However, ARIA is best known in adults and its recommendations should be further disseminated in pediatrics [4,6,7,19,20,26].…”

“…As stated by ARIA guidelines, AR may be classified as intermittent or persistent, while severity of disease may be rated as mild, moderate, or severe [6,7].The former classification that included seasonal and perennial AR is no longer recommended [4,6,7,[19][20][21][22]26]. AR is still a condition where patients do not always seek appropriate treatment, may remain undertreated and do not adhere well to treatment.…”

“…Rupatadine has dual affinity for histamine H1-receptors and PAF receptors. Rupatadine, as a sgAH, has a lower potential for H1receptor occupancy in the brain compared to first-generation antihistamines and is less likely to produce sedation, somnolence or drowsiness at recommended dosages [13][14][15][16][17][18][19]26]. The antiallergic/anti-inflammatory properties of rupatadine as PAF antagonist have been demonstrated in vitro and in a broad spectrum of pharmacological in vivo models in mice, rats, guinea pigs, rabbits, dogs and humans [12,15,16].…”