| First Author | Bozza M | Year | 1999 |
| Journal | J Exp Med | Volume | 189 |
| Issue | 2 | Pages | 341-6 |
| PubMed ID | 9892616 | Mgi Jnum | J:52300 |
| Mgi Id | MGI:1328741 | Doi | 10.1084/jem.189.2.341 |
| Citation | Bozza M, et al. (1999) Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med 189(2):341-6 |
| abstractText | 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-/- 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 alpha (TNF-alpha) than did wild-type mice, but normal levels of interleukin (IL)-6 and IL-10. When stimulated with LPS and interferon gamma, macrophages from MIF-/- mice showed diminished production of TNF-alpha, normal IL-6 and IL-12, and increased production of nitric oxide. MIF-/- 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-/- 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. |
