{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:24:33Z","timestamp":1792898673526,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["PRIN PNRR P20225P4T7"],"award-info":[{"award-number":["PRIN PNRR P20225P4T7"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Respiratory tract infections are a major cause of morbidity and mortality. After the SARS-CoV-2 pandemic, pathogenetic mechanisms leading to more severe outcomes were investigated, including uncontrolled viral replication in the upper airways. This was only partially investigated for other respiratory viruses. We measured mucosal expression of IFN-\u03b21, IFN-\u03bb1, IFN-\u03bb2\/3, IL-1\u03b2, and IL-6 in patients infected by human metapneumovirus, human rhinovirus, human respiratory syncytial virus or type A influenza virus. A total of 806 nasopharyngeal swabs were collected from patients presenting at emergency departments or hospitalized. Viral load was inferred through cycle threshold determination, whereas cytokine levels were measured through mRNA detection. Each expression pattern was correlated with age, viral load, and specific infecting virus. IFN-\u03b21 and IFN-\u03bb2\/3 showed a negative correlation with viral load, while IFN-\u03bb1 and IL-6 exhibited the opposite trend, suggesting increased inflammation with higher viral load. This was more evident in the \u226570-year-old group, with significantly higher IL-6 levels. Higher viral load of potentially more pathogenic viruses was associated with higher IL-6 expression. Cytokine production in the upper respiratory tract is only partially influenced by age per se, with a more relevant role played by viral load and specific infecting virus. In older patients, this response is less coordinated and prone to elicit a proinflammatory response, especially when clinically impacting viruses are involved.<\/jats:p>","DOI":"10.3390\/biom15111545","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expression Patterns of Interferons and Proinflammatory Cytokines in the Upper Respiratory Tract of Patients Infected by Different Viral Pathogens: Correlation with Age and Viral Load"],"prefix":"10.3390","volume":"15","author":[{"given":"Roberto","family":"Ferrarese","sequence":"first","affiliation":[{"name":"Department of Medicine and Technological innovation (DIMIT), University of Insubria, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2741-8840","authenticated-orcid":false,"given":"Federica","family":"Novazzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological innovation (DIMIT), University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Medical Microbiology and Virology, University Hospital of Varese, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Arcari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological innovation (DIMIT), University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Medical Microbiology and Virology, University Hospital of Varese, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Genoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological innovation (DIMIT), University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Medical Microbiology and Virology, University Hospital of Varese, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-0703","authenticated-orcid":false,"given":"Francesca","family":"Drago Ferrante","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Microbiology and Virology, University Hospital of Varese, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-9861","authenticated-orcid":false,"given":"Nicola","family":"Clementi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"IRCCS San Raffaele Hospital, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Messali","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"},{"name":"Institute of Microbiology, ASST-Spedali Civili, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino Maria Guglielmo","family":"Pitrolo","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-9033","authenticated-orcid":false,"given":"Francesca","family":"Caccuri","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-2579","authenticated-orcid":false,"given":"Antonio","family":"Piralla","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"},{"name":"Institute of Microbiology, ASST-Spedali Civili, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicasio","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological innovation (DIMIT), University of Insubria, 21100 Varese, Italy"},{"name":"Laboratory of Medical Microbiology and Virology, University Hospital of Varese, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e35841","DOI":"10.1016\/j.heliyon.2024.e35841","article-title":"Global epidemiological trends in the incidence and deaths of acute respiratory infections from 1990 to 2021","volume":"10","author":"Chen","year":"2024","journal-title":"Heliyon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e33354","DOI":"10.7554\/eLife.33354","article-title":"IFN-\u03bb prevents influenza virus spread from the upper airways to 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