• Karlhans F Che, Sara Tengvall, Bettina Levänen, Elin Silverpil, Margaretha E Smith, Muhammed Awad, Max Vikström, Lena Palmberg, Ingemar Qvarfordt, Magnus Sköld, and Anders Lindén.
• 1 Unit for Lung and Airway Research, Institute of Environmental Medicine.
• Am. J. Respir. Crit. Care Med.. 2014 Nov 1;190(9):1022-31.

RationaleThe role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known.ObjectivesTo characterize the role of IL-26 in antibacterial host defense of human lungs.MethodsIntrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro.Measurements And Main ResultsExtracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells.ConclusionsThis study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.

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