Mepolizumab decreases urinary excretion of LTE4 in severe asthma
| Autor: | Nikolaos Lazarinis, Craig E. Wheelock, Apostolos Bossios, Alessandro Quaranta, Javier Zurita, Sven-Erik Dahlén, Valentyna Yasinska, Johan Kolmert, Barbro Dahlén |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
business.industry Urinary system Metabolite Decreased Concentration Prostaglandin Urine respiratory system Eosinophil medicine.disease Gastroenterology chemistry.chemical_compound medicine.anatomical_structure chemistry Internal medicine medicine lipids (amino acids peptides and proteins) business Mepolizumab medicine.drug Asthma |
| Zdroj: | Allergy and immunology. |
| Popis: | Background: Urinary metabolites of cysteinyl-leukotrienes (CysLTs) and prostaglandin (PG) D2 are increased in type 2 asthma. The eosinophil is one source of the CysLTs, whereas most PGD2 is biosynthesised in mast cells. It is not known if treatment with anti-interleukin(IL)-5 affects urinary LTE4, the main metabolite of the CysLTs. Aim: To assess if treatment with mepolizumab (Mepo) affects urinary LTE4 and the two main metabolites of PGD2, 2,3-dinor-11β-PGF2α and tetranor-PGDM. Methods: Clinical examinations of 23 subjects (12 men and 11 women, mean age 53 [range 35-75]) with severe asthma, meeting the Swedish guideline criteria for treatment with Mepo (100 mg sc every 4th week), were performed before treatment and at follow-up visits 4 and 12 months later. Urine collected at all visits was analysed by mass spectrometry. Results: Mepo treatment progressively improved lung function, FENO and ACQ-6, while reducing use of oral corticosteroids (OCS; Table 1). Blood eosinophils were reduced by 85% and urinary LTE4 by 67% at 12 months (Table 1), whereas urinary PGD2 metabolites and serum tryptase did not significantly change (Table 1). Conclusion: The study for the first time documents that reduction of blood eosinophils results in decreased concentration of urinary LTE4. This supports that the eosinophil is the major source of increased CysLTs in asthma, suggesting that the therapeutic response to Mepo may also involve decreased production of CysLTs. |
| Databáze: | OpenAIRE |
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