{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:51:13Z","timestamp":1790628673242,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"Children's Miracle Network","award":["CMN-FY19-Halstead"],"award-info":[{"award-number":["CMN-FY19-Halstead"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p> Inhaled granulocyte\/macrophage colony-stimulating factor (GM-CSF) shows promise as a therapeutic to treat viral and bacterial pneumonia, but no mouse model of inhaled GM-CSF has been described. We sought to 1) develop a mouse model of aerosolized recombinant mouse GM-CSF administration and 2) investigate the protection conferred by inhaled GM-CSF during influenza A virus (IAV) infection against secondary bacterial infection with pneumococcus. To assess lower respiratory tract delivery of aerosolized therapeutics, mice were exposed to aerosolized fluorescein (FITC)-labeled dextran noninvasively via an aerosolization tower or invasively using a rodent ventilator. The efficiency of delivery to the lower respiratory tracts of mice was 0.01% noninvasively compared with 0.3% invasively. The airway pharmacokinetics of inhaled GM-CSF fit a two-compartment model with a terminal phase half-life of 1.3 h. To test if lower respiratory tract levels were sufficient for biological effect, mice were infected intranasally with IAV, treated with aerosolized recombinant mouse GM-CSF, and then secondarily infected with Streptococcus pneumoniae. Inhaled GM-CSF conferred a significant survival benefit to mice against secondary challenge with S. pneumoniae ( P &lt; 0.05). Inhaled GM-CSF did not reduce airway or lung parenchymal bacterial growth but significantly reduced the incidence of S. pneumoniae bacteremia ( P &lt; 0.01). However, GM-CSF overexpression during influenza virus infection did not affect lung epithelial permeability to FITC-dextran ingress into the bloodstream. Therefore, the mechanism of protection conferred by inhaled GM-CSF appears to be locally mediated improved lung antibacterial resistance to systemic bacteremia during IAV infection. <\/jats:p>","DOI":"10.1152\/ajplung.00296.2019","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T14:22:22Z","timestamp":1580307742000},"page":"L571-L579","source":"Crossref","is-referenced-by-count":29,"title":["Lower respiratory tract delivery, airway clearance, and preclinical efficacy of inhaled GM-CSF in a postinfluenza pneumococcal pneumonia model"],"prefix":"10.1152","volume":"318","author":[{"given":"Todd M.","family":"Umstead","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eranda Kurundu","family":"Hewage","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Mathewson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Beaudoin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zissis C.","family":"Chroneos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1167-0363","authenticated-orcid":false,"given":"E. Scott","family":"Halstead","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"},{"name":"Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","first-page":"487","volume":"43","author":"Amirav I","year":"2002","journal-title":"J Nucl Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9074-6"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit653"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300014"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3109\/01902149409031739"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00503.2018"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1979.47.6.1315"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00132.2019"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-017-0708-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/BF01704742"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201311-2041LE"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201012-2036OC"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1997.273.4.L715"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0906695"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir522"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.5.2203"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3109\/08958378.2011.632787"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01892.x"},{"key":"B19","first-page":"1","volume-title":"Pulmonary Physiology","author":"Levitzky MG","year":"2013","edition":"8"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00654-11"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3231"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5001"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31822d7bf0"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-0774"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1999.276.4.L556"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3182416f23"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00343.2014"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004053"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.08.022"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq021"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003238"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit830"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nm1765"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01922"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200906-0978OC"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01322.2009"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax3387"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.09.004"},{"key":"B39","first-page":"319","volume":"49","author":"Ullman-Culler\u00e9 MH","year":"1999","journal-title":"Lab Anim Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62139"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.06.010"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4161\/21688370.2014.982424"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b07524"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajplung.00296.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T23:19:13Z","timestamp":1584659953000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajplung.00296.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4,1]]}},"alternative-id":["10.1152\/ajplung.00296.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00296.2019","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}