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Respir Res. 2013 Jul 3;14:69. doi: 10.1186/1465-9921-14-69.

NF-κB activation in myeloid cells mediates ventilator-induced lung injury.

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1
Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.

Abstract

BACKGROUND:

Although use of the mechanical ventilator is a life-saving intervention, excessive tidal volumes will activate NF-κB in the lung with subsequent induction of lung edema formation, neutrophil infiltration and proinflammatory cytokine/chemokine release. The roles of NF-κB and IL-6 in ventilator-induced lung injury (VILI) remain widely debated.

METHODS:

To study the molecular mechanisms of the pathogenesis of VILI, mice with a deletion of IкB kinase in the myeloid cells (IKKβ(Δmye)), IL-6(-/-) to WT chimeric mice, and C57BL/6 mice (WT) were placed on a ventilator for 6 hr.WT mice were also given an IL-6-blocking antibody to examine the role of IL-6 in VILI.

RESULTS:

Our results revealed that high tidal volume ventilation induced pulmonary capillary permeability, neutrophil sequestration, macrophage drifting as well as increased protein in bronchoalveolar lavage fluid (BALF). IL-6 production and IL-1β, CXCR2, and MIP2 expression were also increased in WT lungs but not in those pretreated with IL-6-blocking antibodies. Further, ventilator-induced protein concentrations and total cells in BALF, as well as lung permeability, were all significantly decreased in IKKβ(Δmye) mice as well as in IL6(-/-) to WT chimeric mice.

CONCLUSION:

Given that IKKβ(Δmye) mice demonstrated a significant decrease in ventilator-induced IL-6 production, we conclude that NF-κB-IL-6 signaling pathways induce inflammation, contributing to VILI, and IкB kinase in the myeloid cells mediates ventilator-induced IL-6 production, inflammation, and lung injury.

PMID:
23822633
PMCID:
PMC3708752
DOI:
10.1186/1465-9921-14-69
[Indexed for MEDLINE]
Free PMC Article
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