{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:06:25Z","timestamp":1791950785382,"version":"4.3.4"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To determine whether the serum levels of leptin are altered in patients with ECRS.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient\u2019s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin <jats:italic>in vitro<\/jats:italic> to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001 vs. ECRS; <jats:italic>p<\/jats:italic> &amp;lt; 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, <jats:italic>p<\/jats:italic> &amp;lt; 0.01) and the number of eosinophils in NPs (r = 0.5109, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, <jats:italic>p<\/jats:italic> &amp;lt; 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established <jats:italic>in vitro<\/jats:italic> from NPs in a leptin receptor-dependent manner (<jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.<\/jats:p>","DOI":"10.3389\/fphar.2021.793607","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T08:44:45Z","timestamp":1641199485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Yoshimasa","family":"Imoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeharu","family":"Ueki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukinori","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyo","family":"Morikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kidoguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Tsutsumiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Ogi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Sakashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takechiyo","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Schleimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Takabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeharu","family":"Fujieda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1111\/all.14235","article-title":"Efficacy and Safety of Treatment with Biologicals (Benralizumab, Dupilumab and Omalizumab) for Severe Allergic Asthma: A Systematic Review for the EAACI Guidelines - Recommendations on the Use of Biologicals in Severe Asthma","volume":"75","author":"Agache","year":"2020","journal-title":"Allergy"},{"key":"B2","doi-asserted-by":"publisher","first-page":"279","DOI":"10.2500\/105065800781329573","article-title":"Nasal Polyposis: From Cytokines to Growth","volume":"14","author":"Bachert","year":"2000","journal-title":"Am. 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