{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:56:20Z","timestamp":1793318180432,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":402,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Influenza is a highly contagious, acute respiratory disease that causes significant public health and economic threats. Influenza infection induces various inflammatory mediators, IFNs, and recruitment of inflammatory cells in the host. This inflammatory \u201ccytokine storm\u201d is thought to play a role in influenza-induced lung pathogenesis. Empagliflozin is a drug primarily used to lower blood glucose in type II diabetes patients by inhibiting the sodium\u2013glucose cotransporter-2 (SGLT-2) found in the proximal tubules in the kidneys. In this study, we have investigated the effects of empagliflozin on the pulmonary immune response to influenza infection. C57BL\/6 mice (wild type) were infected with influenza A\/PR\/8\/34 and treated with empagliflozin, and the disease outcomes were analyzed. Empagliflozin treatment decreased the expression of the inflammatory cytokines IL-1\u03b2, IL-6, and CCL2; the percentage of inflammatory monocytes and inducible NO synthase\u2013positive macrophages; and IFN response genes Stat1 and CXCL9 during influenza infection. Further, empagliflozin treatment decreases the expression of IL-6, CCL2, and CCL5 in RAW264.7 macrophages and bone marrow\u2013derived macrophages. However, empagliflozin treatment increased influenza viral titer during infection. Despite fostering an increased viral burden, treatment with empagliflozin decreases the mortality in wild type and high fat diet\u2013induced atherosclerotic LDLR\u2212\/\u2212 mice. Based on our findings, empagliflozin may have therapeutic implications for use in patients to prevent lung damage and acute respiratory illness.<\/jats:p>","DOI":"10.4049\/immunohorizons.2300077","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T13:47:13Z","timestamp":1702993633000},"page":"861-871","source":"Crossref","is-referenced-by-count":9,"title":["Sodium\u2013Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1102-8251","authenticated-orcid":false,"given":"Nicholas J","family":"Constantinesco","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-2303","authenticated-orcid":false,"given":"Baskaran","family":"Chinnappan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J","family":"DeVito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7776-0051","authenticated-orcid":false,"given":"Crystal","family":"Moras","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6946-4570","authenticated-orcid":false,"given":"Sashwath","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria de la Luz","family":"Garcia-Hernandez","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-1182","authenticated-orcid":false,"given":"Javier","family":"Rangel-Moreno","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester , Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-5744","authenticated-orcid":false,"given":"Radha","family":"Gopal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children\u2019s Hospital of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"2025010607440206000_r1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. 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