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We asked whether release of IL-12 is part of the normal host response to this infection and whether local treatment with IL-12 or gene transfer of IL-12 could accelerate clearance of infection. IL-12 was assayed by enzyme-linked immunosorbent assay in normal mice and in mice deficient in IL-12 after inoculation of<jats:italic>Pneumocystis carinii<\/jats:italic>.<jats:italic>P. carinii<\/jats:italic>-infected mice were treated with local instillation of IL-12 and gene transfer of the IL-12 gene. Inoculation of<jats:italic>P. carinii<\/jats:italic>into normal mice evoked a brisk release of IL-12 into lung tissue, and IL-12 P35-deficient mice showed delayed clearance of infection measured by PCR for<jats:italic>P. carinii<\/jats:italic>rRNA. In control mice, intranasal recombinant IL-12 accelerated clearance of infection, and this was associated with increased recruitment of inflammatory cells into lavage fluid and increased release of tumor necrosis factor alpha, IL-12, and gamma interferon. Similar results were observed in infected mice depleted of CD4<jats:sup>+<\/jats:sup>lymphocytes by using in vivo transfer of the IL-12 gene in a replication-deficient adenoviral vector. IL-12 is part of the normal host response to infection with<jats:italic>P. carinii<\/jats:italic>. IL-12 therapy can enhance host resistance to infection in both normal mice and mice depleted of CD4<jats:sup>+<\/jats:sup>T lymphocytes. A treatment effect of IL-12 is mediated through enhanced inflammatory cell recruitment into lung tissue and increased tissue concentrations of proinflammatory cytokines.<\/jats:p>","DOI":"10.1128\/iai.00065-08","type":"journal-article","created":{"date-parts":[[2008,3,11]],"date-time":"2008-03-11T01:05:47Z","timestamp":1205197547000},"page":"2130-2137","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Interleukin-12 and Host Defense against Murine<i>Pneumocystis<\/i>Pneumonia"],"prefix":"10.1128","volume":"76","author":[{"given":"Sanbao","family":"Ruan","sequence":"first","affiliation":[{"name":"Section of Pulmonary\/Critical Care Medicine, LSU Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"McKinley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingquan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Rudner","sequence":"additional","affiliation":[{"name":"Section of Pulmonary\/Critical Care Medicine, LSU Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Section of Pulmonary\/Critical Care Medicine, LSU Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K.","family":"Kolls","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judd E.","family":"Shellito","sequence":"additional","affiliation":[{"name":"Section of Pulmonary\/Critical Care Medicine, LSU Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/314996"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/5.2.186"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.103.2_Supplement.116S-a"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5102"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/301527a0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1996.7.3-333"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.1997.tb00184.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1994.tb01514.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.11.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000168974.67090.70"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1994.10.1619"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.2306-2311.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.4049\/jimmunol.155.5.2515","volume":"155","year":"1995","unstructured":"Flynn, J. 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