{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:07:44Z","timestamp":1791274064163,"version":"4.1.0"},"reference-count":31,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,1,18]]},"abstract":"<jats:p>To study the biologic role of migration inhibitory factor (MIF), a pleiotropic cytokine, we generated a mouse strain lacking MIF by gene targeting in embryonic stem cells. Analysis of the role of MIF during sepsis showed that MIF\u2212\/\u2212 mice were resistant to the lethal effects of high dose bacterial lipopolysaccharide (LPS), or Staphylococcus aureus enterotoxin B (SEB) with d-galactosamine and had lower plasma levels of tumor necrosis factor \u03b1 (TNF-\u03b1) than did wild-type mice, but normal levels of interleukin (IL)-6 and IL-10. When stimulated with LPS and interferon \u03b3, macrophages from MIF\u2212\/\u2212 mice showed diminished production of TNF-\u03b1, normal IL-6 and IL-12, and increased production of nitric oxide. MIF\u2212\/\u2212 animals cleared gram-negative bacteria Pseudomonas aeruginosa instilled into the trachea better than did wild-type mice and had diminished neutrophil accumulation in their bronchoalveolar fluid compared to the wild-type mice. Thioglycollate elicited peritoneal exudates in uninfected MIF\u2212\/\u2212 mice, but showed normal neutrophil accumulation. Finally, the findings of enhanced resistance to P. aeruginosa and resistance to endotoxin-induced lethal shock suggest that the counteraction or neutralization of MIF may serve as an adjunct therapy in sepsis.<\/jats:p>","DOI":"10.1084\/jem.189.2.341","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"341-346","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":443,"title":["Targeted Disruption of Migration Inhibitory Factor Gene Reveals Its Critical Role in Sepsis"],"prefix":"10.1084","volume":"189","author":[{"given":"Marcelo","family":"Bozza","sequence":"first","affiliation":[{"name":"From the *Department of Immunology and Infectious Diseases, Harvard School of Public Health, and the \u2021Ina Sue Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts 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