{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:02:20Z","timestamp":1786122140046,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["VE 842\/5-1"],"award-info":[{"award-number":["VE 842\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"award":["VE 842\/5-1"],"award-info":[{"award-number":["VE 842\/5-1"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Adv. Respir. Med.","ARM"],"abstract":"<jats:p>Background: Bronchial asthma is a chronic inflammatory airway disease characterized by acute bronchoconstriction and type 2-driven inflammation. This study investigated whether inhaled amitriptyline, a functional inhibitor of acid sphingomyelinase, exerts both bronchodilatory and immunomodulatory effects in experimental murine models of allergic airway inflammation (AAI) and human cellular systems. Methods: Acute AAI was induced in mice using ovalbumin (OVA) and house dust mite (HDM) protocols, respectively. Inhaled amitriptyline (3.3 mg\/mL) was administered for either 20 days (short-term) or 36 days (long-term). Lung function was assessed using FlexiVent\u00ae, and inflammatory markers including IgE, eosinophils, and type 2 cytokines were measured in bronchoalveolar lavage fluid and lung tissue. Complementary experiments were included using passively sensitized PCLSs and human type 2-differentiated CD4+ T cells. Results: Inhaled amitriptyline improved lung mechanics in both the OVA and HDM models, reducing total respiratory resistance and elastance. In the OVA model, eosinophil and T cell counts in BALF were decreased, whereas immunomodulatory effects were less pronounced in the short-term HDM model. In human TH2 cells, no significant changes in cytokine production or gene expression were observed. Ex vivo, amitriptyline dose-dependently inhibited allergen-induced bronchoconstriction in PCLSs. Conclusions: Inhaled amitriptyline improves lung function across murine models of AAI, supporting its potential in exhibiting model-dependent immunomodulatory effects, and directly attenuates allergen-induced bronchoconstriction, supporting its potential as a bronchodilator with context-dependent immunomodulatory properties.<\/jats:p>","DOI":"10.3390\/arm94040058","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:52:30Z","timestamp":1786031550000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Inhaled Amitriptyline on Airway Function and Immune Responses in Experimental Asthma"],"prefix":"10.3390","volume":"94","author":[{"given":"Anna","family":"Michely","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"},{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"B\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"},{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Ben Hamza","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Rachimow","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3566-227X","authenticated-orcid":false,"given":"Klaus","family":"Tenbrock","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Verjans","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"},{"name":"Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2002094","DOI":"10.1183\/13993003.02094-2020","article-title":"Trends in worldwide asthma prevalence","volume":"56","author":"Asher","year":"2020","journal-title":"Eur. 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