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Viral infections lead to an inflammatory response that includes elevated levels of IL\u20106 and interferons. IL\u20106 activates the JAK\/STAT signaling pathway, amplifying downstream inflammation. Given the clinical efficacy of the JAK inhibitor baricitinib in reducing disease severity in COVID\u201019, we evaluated its impact in a murine model of influenza, MRSA, and post\u2010influenza MRSA pneumonia. Additionally, because IL\u20106 inhibitory therapies have improved outcomes during COVID\u201019, we evaluated the impact of IL\u20106 deletion on post\u2010influenza MRSA pneumonia. In our studies, baricitinib effectively inhibited the JAK\/STAT pathway in the lungs, as demonstrated by decreased interferon\u2010stimulated genes (ISGs) and STAT3 phosphorylation. Despite this inhibition, baricitinib did not cause a global suppression of cytokines. Notably, baricitinib treatment did not impair either antiviral or antibacterial host immunity, inflammatory cell recruitment, or lung tissue injury. IL\u20106 deficiency did not alter weight loss, inflammatory cell recruitment, or bacterial burden during post\u2010influenza MRSA pneumonia. These findings suggest that both JAK inhibition via baricitinib and IL\u20106 deletion do not enhance host defense or limit tissue injury in murine models of influenza and post\u2010influenza MRSA pneumonia.<\/jats:p>","DOI":"10.14814\/phy2.70232","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:28:11Z","timestamp":1739251691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic <scp>JAK<\/scp> inhibition does not impact lung injury during viral or bacterial pneumonia in male mice"],"prefix":"10.14814","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-9029","authenticated-orcid":false,"given":"Lokesh","family":"Sharma","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania 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M.","family":"Duray","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathanial J.","family":"Tolman","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan J.","family":"McVerry","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles S.","family":"Dela Cruz","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Pediatrics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-0552","authenticated-orcid":false,"given":"William","family":"Bain","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7896-6426","authenticated-orcid":false,"given":"Keven M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine University of Pittsburgh  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