A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF‐α

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Abstract
The T‐cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airwaysin vivoand may thus constitute a link between activation of T‐lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)‐α.In vitro, human (h) IL-17 concentration-dependently stimulated the release of GM-CSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cellsin vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF‐α potentiated the release of GM-CSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF‐α. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF‐α prolonged survival (trypan blue exclusion) of human neutrophilsin vitroand this effect was blocked by an anti-GM-CSF antibody.In vivo, local co-stimulation with mouse IL-17 plus TNF‐α caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti‐GM-CSF antibody given systemically.In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor‐α, probablyviaeffects on both recruitment and survival of neutrophils.