{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:33Z","timestamp":1790837073446,"version":"4.1.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012754","name":"Horizon Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012754","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stacy True Memorial Trust Fund"},{"name":"NIH\/NCATS","award":["UL1TR002535"],"award-info":[{"award-number":["UL1TR002535"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    The cytokine Interferon-\u03b3 (IFN-\u03b3) exerts powerful immunoregulatory effects on the adaptive immune system and also enhances functions of the neutrophil (PMN). The clinical use of IFN-\u03b3 has been driven by the finding that its administration to patients with chronic granulomatous disease (CGD) results in decreased incidence and severity of infections. However, IFN-\u03b3 has no effect on the characteristic defect of CGD, the inability to convert oxygen to microbicidal metabolites including superoxide anion (O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>-<\/jats:sup>\n                    ) during the phagocytosis associated oxidative burst. We administered varying doses of IFN-\u03b3 to adult volunteers and studied the effects on plasma drug levels and response molecules and PMNs isolated from blood drawn at intervals over a 96- hour period. Plasma concentrations of IFN-\u03b3, IP-10 and neopterin, and stimulated release of O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>-<\/jats:sup>\n                    from PMNs exhibited dose- and time-dependent increases after IFN-\u03b3 administration. Gene expression in PMNs was altered for 2775 genes; changes occurred rapidly after administration and returned to baseline in 24\u201336 hours. Several genes involved with neutrophil host defense were upregulated including those for components of the O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>-<\/jats:sup>\n                    generating NADPH oxidase; innate-immune and Fc receptors; proteins involved in MHCI and II; a regulator of circulating PMN number; guanylate binding proteins; and a key enzyme in synthesis of an essential NOS cofactor. Coordinate changes were detected in protein levels of representative products from several of these genes. Lysates from isolated neutrophils also demonstrated a spike in NO following IFN-\u03b3 administration. IFN-\u03b3 appears to increase non-oxygen dependent microbicidal functions of PMNs which could provide strategies to compensate for deficiencies, explain its clinical benefit for CGD patients and expand therapeutic applications of IFN-\u03b3 to other disorders.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial registration:<\/jats:bold>\n                    Protocol registered in ClinicalTrials.gov,\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT02609932\" xlink:type=\"simple\">NCT02609932<\/jats:ext-link>\n                    , Effect of IFN-\u03b3 on Innate Immune Cells.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0263370","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T13:51:47Z","timestamp":1643896307000},"page":"e0263370","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["In vivo interferon-gamma induced changes in gene expression dramatically alter neutrophil phenotype"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-354X","authenticated-orcid":true,"given":"Daniel R.","family":"Ambruso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-9552","authenticated-orcid":true,"given":"Natalie J.","family":"Briones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5147-073X","authenticated-orcid":true,"given":"Angelina F.","family":"Baroffio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9360-4481","authenticated-orcid":true,"given":"John R.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-7611","authenticated-orcid":true,"given":"Alexander D.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Gowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-0198","authenticated-orcid":true,"given":"Bridget","family":"Sanford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ellison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"pone.0263370.ref001","first-page":"123","article-title":"Interferon-gamma and systemic autoimmunity","volume":"16","author":"KM Pollard","year":"2013","journal-title":"Discov Med"},{"key":"pone.0263370.ref002","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0065-2776(07)96002-2","article-title":"Regulation of interferon-gamma during innate and adaptive immune responses","volume":"96","author":"JR Schoenborn","year":"2007","journal-title":"Adv Immunol"},{"key":"pone.0263370.ref003","doi-asserted-by":"crossref","first-page":"13925","DOI":"10.1074\/jbc.R116.774745","article-title":"Current prospects of type II interferon gamma signaling and autoimmunity","volume":"292","author":"DS Green","year":"2017","journal-title":"J Biol Chem"},{"key":"pone.0263370.ref004","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1365-2567.2004.01849.x","article-title":"Interferon-\u03b3 activation of polymorphonuclear neutrophil function","volume":"112","author":"TN Ellis","year":"2004","journal-title":"Immunology"},{"key":"pone.0263370.ref005","doi-asserted-by":"crossref","first-page":"e0185956","DOI":"10.1371\/journal.pone.0185956","article-title":"IFN-gamma alters the expression of diverse immunity related genes in a cell culture model designed to represent maturing neutrophils","volume":"12","author":"MA Ellison","year":"2017","journal-title":"PLoS.One"},{"key":"pone.0263370.ref006","volume-title":"Kendig and Chernick\u2019s Disorders of the Respiratory Tract in Children","author":"DR Ambruso","year":"2012"},{"key":"pone.0263370.ref007","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJM199102213240801","article-title":"A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. 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