RGD Reference Report - Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. - Rat Genome Database

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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 
Citation: Wirtz S, etal., J Exp Med. 2006 Aug 7;203(8):1875-81. doi: 10.1084/jem.20060471. Epub 2006 Jul 31.
RGD ID: 126790504
Pubmed: PMID:16880260   (View Abstract at PubMed)
PMCID: PMC2118378   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20060471   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Septic Peritonitis exacerbatesISOIl27 (Mus musculus)126790504; 126790504 RGD 
Septic Peritonitis exacerbatesIMP 126790504 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)

Additional Information