• Ju Cao, Fang Xu, Shihui Lin, Zhixin Song, Lipin Zhang, Peng Luo, Huajian Xu, Dairong Li, Ke Zheng, Guosheng Ren, and Yibing Yin.
• Department of Laboratory Medicine, The Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
• Thorax. 2014 Oct 1;69(10):926-37.

BackgroundInterleukin 27 (IL-27) is an important cytokine regulating host immune responses. However, its role in sepsis-induced immunosuppression remains unclear.AimTo 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.MethodsCLP 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.ResultsIL-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.ConclusionsIL-27 is an important mediator of sepsis-induced impairment of lung antibacterial host defence.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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