Details

Autor(en) / Beteiligte

• Wirtz, Stefan
• Tubbe, Ingrid
• Galle, Peter R
• Schild, Hans J
• Birkenbach, Mark
• Blumberg, Richard S
• Neurath, Markus F

Titel

Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27

Ist Teil von

• The Journal of experimental medicine, 2006-08, Vol.203 (8), p.1875-1881

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.