| First Author | Wirtz S | Year | 2006 |
| Journal | J Exp Med | Volume | 203 |
| Issue | 8 | Pages | 1875-81 |
| PubMed ID | 16880260 | Mgi Jnum | J:124391 |
| Mgi Id | MGI:3721463 | Doi | 10.1084/jem.20060471 |
| Citation | Wirtz S, et al. (2006) Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J Exp Med 203(8):1875-81 |
| abstractText | The immune response to bacterial infections must be tightly controlled to guarantee pathogen elimination while preventing tissue damage by uncontrolled inflammation. Here, we demonstrate a key role of interleukin (IL)-27 in regulating this critical balance. IL-27 was rapidly induced during murine experimental peritonitis induced by cecal ligation and puncture (CLP). Furthermore, mice deficient for the EBI3 subunit of IL-27 were resistant to CLP-induced septic peritonitis as compared with wild-type controls, and this effect could be suppressed by injection of recombinant single-chain IL-27. EBI3-/- mice displayed significantly enhanced neutrophil migration and oxidative burst capacity during CLP, resulting in enhanced bacterial clearance and local control of infection. Subsequent studies demonstrated that IL-27 directly suppresses endotoxin-induced production of reactive oxygen intermediates by isolated primary granulocytes and macrophages. Finally, in vivo blockade of IL-27 function using a newly designed soluble IL-27 receptor fusion protein led to significantly increased survival after CLP as compared with control-treated mice. Collectively, these data identify IL-27 as a key negative regulator of innate immune cell function in septic peritonitis. Furthermore, in vivo blockade of IL-27 is a novel potential therapeutic target for treatment of sepsis. |
