{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:11:55Z","timestamp":1789542715275,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria is necessary to control infection, but it may also contribute to tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact of ROL in a pneumococcal pneumonia murine model. Mice were infected intranasally with 105\u2013106 CFU of Streptococcus pneumoniae, treated with ROL in a prophylactic or therapeutic schedule in combination, or not, with the antibiotic ceftriaxone. Inflammation and bacteria counts were assessed, and ex vivo phagocytosis assays were performed. ROL treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs and airways and reduced lung injury. Prophylactic ROL treatment also decreased cytokine levels in the airways. Although modulation of inflammation by ROL ameliorated pneumonia, bacteria burden was not reduced. On the other hand, antibiotic therapy reduced bacteria without reducing neutrophil infiltration, cytokine level, or lung injury. Combined ROL and ceftriaxone treatment decreased lethality rates and was more efficient in reducing inflammation, by increasing proresolving protein annexin A1 (AnxA1) expression, and bacterial burden by enhancing phagocytosis. Lack of AnxA1 increased inflammation and lethality induced by pneumococcal infection. These data show that immunomodulatory effects of phosphodiesterase-4 inhibitors are useful during severe pneumococcal pneumonia and suggest their potential benefit as adjunctive therapy during infectious diseases.<\/jats:p>","DOI":"10.1165\/rcmb.2015-0083oc","type":"journal-article","created":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T17:10:15Z","timestamp":1450372215000},"page":"24-34","source":"Crossref","is-referenced-by-count":42,"title":["Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice"],"prefix":"10.1093","volume":"55","author":[{"given":"Luciana P.","family":"Tavares","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana C.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de V\u00edrus Respirat\u00f3rios e do Sarampo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana P.","family":"Vago","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso M.","family":"Queiroz-Junior","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna A.","family":"David","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milene A.","family":"Rachid","sequence":"additional","affiliation":[{"name":"Departamento de Patologia Geral, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia M. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo C.","family":"Russo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"Laborat\u00f3rio de Imunologia e Mec\u00e2nica Pulmonar, Departamento de Fisiologia e Biof\u00edsica, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirl\u00e2ndia P.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,7,1]]},"reference":[{"key":"2026021122402707600_bib1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/1471-2334-14-335","article-title":"Microbial aetiology, 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