Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by severe, sometimes life-threatening reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Mechanisms driving the disease include overproduction of leukotrienes and loss of anti-inflammatory prostaglandin E (PGE) production. Many cell types contribute to the disease; however, eosinophils are markedly elevated and are important drivers of pathologic findings.
Objective: To investigate the capacity of aspirin and NSAIDs to drive eosinophil activation and the ability of PGE to inhibit this activation.
Methods: Eosinophils were purified from blood of healthy individuals without AERD and stimulated with lysine aspirin, ketorolac, or sodium salicylate. The role of PGE in altering activation was determined by incubating eosinophils with increasing doses of PGE before lysine aspirin stimulation. Specific PGE receptor use was determined by incubating eosinophils with receptor agonists and antagonists before aspirin stimulation. Cysteinyl leukotrienes (CysLTs), leukotriene B (LTB), and eosinophil-derived neurotoxin (EDN) were quantified by enzyme-linked immunosorbent assay.
Results: Stimulation of eosinophils with lysine aspirin, ketorolac, or sodium salicylate resulted in secretion of CysLTs and LTB in the absence of EDN release. Low doses of PGE inhibited LTB and CysLT release, an effect lost at higher PGE concentrations. Use of butaprost, an EP receptor agonist, suppressed lysine aspirin stimulation. This mechanism was supported by blocking activity of the EP and EP receptors.
Conclusion: Eosinophils can be directly activated by NSAIDs via cyclooxygenase-independent pathways to produce CysLTs and LTB. This effect can be inhibited by PGE acting through the EP receptor. The recognized loss of EP receptor expression combined with low PGE levels explains in part the sensitivity to NSAIDs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825585 | PMC |
| http://dx.doi.org/10.1016/j.anai.2019.09.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glucagon-like Peptide-1 Receptor Pathway Attenuates Platelet Activation in Aspirin-Exacerbated Respiratory Disease.
J Immunol
December 2023
Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.
Article Synopsis
- Platelets play a significant role in allergic asthma and aspirin-exacerbated respiratory disease (AERD) by being activated and influencing inflammatory responses.
- The study found that the GLP-1 receptor (GLP-1R) agonist liraglutide reduced platelet activation and airway resistance in a mouse model of AERD, indicating its potential therapeutic benefits.
- Liraglutide showed promise in inhibiting platelet activation in both mice and human patients with AERD, suggesting that targeting the GLP-1R could be a new strategy for managing asthma-related inflammation.
Effects of intravenous lysine acetylsalicylate versus oral aspirin on platelet responsiveness in patients with ST-segment elevation myocardial infarction: the ECCLIPSE-STEMI trial.
J Thromb Thrombolysis
February 2023
Cardiovascular Institute, San Carlos University Hospital, Profesor Martin Lagos S/N. 28040, Madrid, Spain.
Prasugrel and ticagrelor, new P2Y12-ADP receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events in patients with an acute coronary syndrome. However, evidence is lacked about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared to oral aspirin. Recently, we demonstrated in healthy volunteers that the administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin.
View Article and Find Full Text PDFCross-reactivity between nonsteroidal anti-inflammatory drugs in fixed drug eruption: Two unusual cases and a literature review.
Br J Clin Pharmacol
February 2023
Department of Pharmacology, Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main causes of fixed drug eruption (FDE). Cross-sensitivity between chemically unrelated NSAIDs has been rarely described in FDE. We report herein two cases of NSAID-induced FDE confirmed by oral provocation test (OPT) with a literature review.
View Article and Find Full Text PDFA retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease.
Eur Arch Otorhinolaryngol
May 2022
Department of ENT, Royal National ENT & Eastman Dental Hospitals, 47-49 Huntley St, Bloomsbury, London, WC1E 6DG, UK.
Purpose: Aspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy.
View Article and Find Full Text PDFOral aspirin or low dose of intravenous lysine acetylsalicylate in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.
J Cardiovasc Med (Hagerstown)
July 2021
Division of Cardiology.
Aim: To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI.
Methods: This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!