RGD Reference Report - IL-27 controls sepsis-induced impairment of lung antibacterial host defence. - Rat Genome Database

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IL-27 controls sepsis-induced impairment of lung antibacterial host defence.

Authors: Cao, Ju  Xu, Fang  Lin, Shihui  Song, Zhixin  Zhang, Lipin  Luo, Peng  Xu, Huajian  Li, Dairong  Zheng, Ke  Ren, Guosheng  Yin, Yibing 
Citation: Cao J, etal., Thorax. 2014 Oct;69(10):926-37. doi: 10.1136/thoraxjnl-2014-205777. Epub 2014 Jul 29.
RGD ID: 126790541
Pubmed: PMID:25074706   (View Abstract at PubMed)
DOI: DOI:10.1136/thoraxjnl-2014-205777   (Journal Full-text)

BACKGROUND: Interleukin 27 (IL-27) is an important cytokine regulating host immune responses. However, its role in sepsis-induced immunosuppression remains unclear.
AIM: To investigate the role of IL-27 in modulating sepsis-induced immunosuppression using a murine model of caecal ligation and puncture (CLP)-induced sepsis followed by secondary challenge with Pseudomonas aeruginosa.
METHODS: CLP or sham surgery was performed in wild-type (WT) and IL-27 receptor (IL-27R)/WSX-1 knockout (KO) mice, and then mice were infected with intratracheal P aeruginosa.
RESULTS: IL-27 was upregulated in patients with sepsis and septic mice. Following sepsis and secondary intrapulmonary bacterial challenge, IL-27R KO mice had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice, which was associated with early increased pulmonary cytokine/chemokine production, as well as enhanced neutrophil recruitment to airspaces. Neutralisation of IL-27 in septic mice significantly improved survival and clearance of bacteria from the lungs of septic mice infected with P aeruginosa, and direct application of recombinant IL-27 could increase susceptibility to P aeruginosa infection. The resistance of septic IL-27R KO mice to secondary P aeruginosa infection was abrogated by depletion of alveolar macrophages (AMs) and neutrophils. AMs from septic IL-27R KO mice had higher bacterial uptake and killing capacities, enhanced cytokine/chemokine production, and increased expression of costimulatory molecules compared with those from WT mice, while neutrophils from septic IL-27R KO mice had increased bacterial killing ability and higher expression of adhesion molecule Mac-1 compared with WT neutrophils.
CONCLUSIONS: IL-27 is an important mediator of sepsis-induced impairment of lung antibacterial host defence.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Pseudomonas Infections amelioratesISOIl27 (Mus musculus)126790541; 126790541associated with SepsisRGD 
Pseudomonas Infections amelioratesIMP 126790541associated with SepsisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)

Additional Information