IL-27 controls sepsis-induced impairment of lung antibacterial host defence. Issue 10 (29th July 2014)

• Record Type: Journal Article
• Authors: Cao, Ju; Xu, Fang; Lin, Shihui; Song, Zhixin; Zhang, Lipin; Luo, Peng; Xu, Huajian; Li, Dairong; Zheng, Ke; Ren, Guosheng; Yin, Yibing
• Is Part Of: Thorax. Volume 69:Issue 10(2014)
• Page Start: 926
• Page End: 937
• Publication Date: 2014-07-29
• Subjects: Bacterial Infection -- Pneumonia -- Respiratory Infection; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2014-205777
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : 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.