{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:43:20Z","timestamp":1790016200120,"version":"4.0.1"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC009"],"award-info":[{"award-number":["SRC009"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012536","name":"Leeds Hospital Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012536","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Inflammation is a key driver in the pathogenesis of cystic fibrosis (CF). We assessed the effectiveness of elexacaftor\/tezacaftor\/ivacaftor (ETI) therapy on downregulating systemic and immune cell-derived inflammatory cytokines. We also monitored the impact of ETI therapy on clinical outcome. Adults with CF, heterozygous for F508del (n = 19), were assessed at baseline, one month and three months following ETI therapy, and clinical outcomes were measured, including sweat chloride, lung function, weight, neutrophil count and C-reactive protein (CRP). Cytokine quantifications were measured in serum and following stimulation of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS) and adenosine triphosphate and analysed using LEGEND plex\n                    <jats:sup>\u2122<\/jats:sup>\n                    Human Inflammation Panel 1 by flow cytometry (n = 19). ASC specks were measured in serum and caspase-1 activity and mRNA levels determined from stimulated PBMCs were determined. Patients remained stable over the study period. ETI therapy resulted in decreased sweat chloride concentrations (p &lt; 0.0001), CRP (p = 0.0112) and neutrophil count (p = 0.0216) and increased percent predicted forced expiratory volume (ppFEV1) (p = 0.0399) from baseline to three months, alongside a trend increase in weight. Three months of ETI significantly decreased IL-18 (p&lt; 0.0011, p &lt; 0.0001), IL-1\u03b2 (p&lt;0.0013, p = 0.0476), IL-6 (p = 0.0109, p = 0.0216) and TNF (p = 0.0028, p = 0.0033) levels in CF serum and following PBMCs stimulation respectively. The corresponding mRNA levels were also found to be reduced in stimulated PBMCs, as well as reduced ASC specks and caspase-1 levels, indicative of NLRP3-mediated production of pro-inflammatory cytokines, IL-1\u03b2 and IL-18. While ETI therapy is highly effective at reducing sweat chloride and improving lung function, it also displays potent anti-inflammatory properties, which are likely to contribute to improved long-term clinical outcomes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0304555","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T14:48:42Z","timestamp":1717166922000},"page":"e0304555","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Anti-inflammatory effects of elexacaftor\/tezacaftor\/ivacaftor in adults with cystic fibrosis heterozygous for F508del"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-4815","authenticated-orcid":true,"given":"Heledd 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J.","family":"Clifton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Etherington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinisa","family":"Savic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-1868","authenticated-orcid":true,"given":"Daniel","family":"Peckham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"pone.0304555.ref001","article-title":"Cystic fibrosis","author":"JS 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