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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL27HumanSeptic Peritonitis exacerbatesISOIl27 (Mus musculus) RGD 
Il27RatSeptic Peritonitis exacerbatesISOIl27 (Mus musculus) RGD 
Il27MouseSeptic Peritonitis exacerbatesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)


Additional Information