{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:15:46Z","timestamp":1772928946433,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T00:00:00Z","timestamp":1172707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Th2 cytokines IL-4 and IL-13 mediate allergic pulmonary inflammation and airways hyperreactivity (AHR) in asthma models through signaling dependent upon the IL-4 receptor-\u03b1 chain (IL-4R\u03b1). IL-13 has been further implicated in the overproduction of mucus by the airway epithelium and in lung remodeling that commonly accompanies chronic inflammation. IL-4R\u03b1\u2013deficient mice are resistant to allergen-induced asthma, highlighting the therapeutic promise of selective molecular inhibitors of IL-4R\u03b1. We designed a chemically modified IL-4R\u03b1 antisense oligonucleotide (IL-4R\u03b1 ASO) that specifically inhibits IL-4R\u03b1 protein expression in lung eosinophils, macrophages, dendritic cells, and airway epithelium after inhalation in allergen-challenged mice. Inhalation of IL-4R\u03b1 ASO attenuated allergen-induced AHR, suppressed airway eosinophilia and neutrophilia, and inhibited production of airway Th2 cytokines and chemokines in previously allergen-primed and -challenged mice. Histologic analysis of lungs from these animals demonstrated reduced goblet cell metaplasia and mucus staining that correlated with inhibition of Muc5AC gene expression in lung tissue. Therapeutic administration of inhaled IL-4R\u03b1 ASO in chronically allergen-challenged mice produced a spectrum of anti-inflammatory activity similar to that of systemically administered Dexamethasone with the added benefit of reduced airway neutrophilia. These data support the potential utility of a dual IL-4 and IL-13 oligonucleotide inhibitor in allergy\/asthma, and suggest that local inhibition of IL-4R\u03b1 in the lung is sufficient to suppress allergen-induced pulmonary inflammation and AHR.<\/jats:p>","DOI":"10.1165\/rcmb.2005-0456oc","type":"journal-article","created":{"date-parts":[[2006,9,21]],"date-time":"2006-09-21T21:12:44Z","timestamp":1158873164000},"page":"276-285","source":"Crossref","is-referenced-by-count":95,"title":["Anti-Inflammatory Activity of Inhaled IL-4 Receptor-\u03b1 Antisense Oligonucleotide in Mice"],"prefix":"10.1093","volume":"36","author":[{"given":"James G.","family":"Karras","sequence":"first","affiliation":[{"name":"Departments of Clinical Development, Pharmacokinetics, and Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey R.","family":"Crosby","sequence":"additional","affiliation":[{"name":"Departments of 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