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- Title
Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27.
- Authors
Wirtz, Stefan; Tubbe, Ingrid; Galle, Peter R; Schild, Hans J; Birkenbach, Mark; Blumberg, Richard S; Neurath, Markus F
- Abstract
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.
- Publication
The Journal of experimental medicine, 2006, Vol 203, Issue 8, p1875
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20060471