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Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in <jats:italic>Streptococcus pneumoniae<\/jats:italic> with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with <jats:italic>Streptococcus pneumoniae<\/jats:italic> and 5 controls) to compare with the transcriptional studies in the mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with <jats:italic>Streptococcus pneumoniae<\/jats:italic> and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from <jats:italic>Streptococcus Pneumoniae<\/jats:italic>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13054-024-04956-6","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T03:48:10Z","timestamp":1716954490000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biological effects of corticosteroids on pneumococcal pneumonia in Mice\u2014translational significance"],"prefix":"10.1186","volume":"28","author":[{"given":"Hiroki","family":"Taenaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine D.","family":"Wick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aartik","family":"Sarma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajani","family":"Ghale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazharul","family":"Maishan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey E.","family":"Gotts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Langelier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S.","family":"Calfee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Matthay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"issue":"1","key":"4956_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","volume":"5","author":"MA Matthay","year":"2019","unstructured":"Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS. 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If a patient was able to consent or had a surrogate available, a study physician or research coordinator obtained written informed consent at the time of enrollment. For subjects who could not consent at enrollment, the UCSF IRB granted an initial waiver of informed consent for biospecimen and clinical data collection, as previously described []. The UCSF IRB also approved a full waiver of consent for patients who died prior to regaining an ability provide informed consent, but restricted data sharing for samples collected from these patients. Because some of the subjects included in the present study were enrolled under a waiver of consent, our IRB protocol prohibits the public release of raw sequencing data, which may contain personally identifiable genetic information. The animal experiments were approved by the UCSF Institutional Animal Care and Use Committee (AN189182), were performed in compliance with the National Institute of Health Guide for Care and Use of Laboratory Animals and were reported in accordance with the Animal Research: Report of In Vivo Experiments (ARRIVE) guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and informed consent"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"185"}}