PMC

Levels of proinflammatory cytokines in the lung and BALF in IKKβ^△mye mice. High tidal volume ventilation-induced IL-6 levels in the lung (A) and BALF (B) were decreased in IKKβ^△mye mice when compared with WT mice. IL-1β levels were assayed in the lung (C) and BALF (D) of IKKβ^△mye mice and WT mice. *P<0.05, **P<0.01.

Effect of IL-6-blocking antibody pretreatment on high tidal volume ventilation-induced lung damage in WT mice. The pulmonary microvascular permeability (A), total number of cells in BALF (B), total protein in BALF (C) and neutrophil sequestration (D) in BALF were determined in WT mice with IL-6-blocking antibody treatment. *P<0.05, **P<0.01, ***P<0.001.

Decreased ventilator-induced lung damage in IL6^-/- to WT chimeric mice but not in WT to WT mice. High tidal volume ventilation induced pulmonary microvascular permeability (A), protein concentration of BALF (B), and total number of cells in BALF (C) in WT to WT mice but not in IL6^-/- to WT chimeric mice. *P<0.05, **P<0.01, ***P<0.001.

Mechanical ventilation induced a significant increase of cytokines/chemokines in WT mice but not in IL-6 antibody-treated WT mice. IL-6 antibody pretreatment decreased high tidal volume ventilation-induced IL-6 levels in the lung (A) and BALF (B) of WT mice. IL-6 antibody pretreatment decreased high tidal volume ventilation-induced IL-1β levels in the lung (C) and BALF (D) of WT mice. *P<0.05, **P<0.01, ***P<0.001. (E) IL-6 antibody treatment decreased high stretch ventilation-induced mRNA expression of proinflammatory cytokines (IL-6, IL-1β) and chemokines (CXCR2, ICAM, MIP-2) in the lung.

The mechanical ventilator (MV) induced the levels of IL-6 and IL-1β in the lung and BALF. MV significantly increased the production of IL-6 (A, B) and IL-1β (C, D) in the lung and BALF, respectively. *P<0.05, **P<0.01, ***P<0.001. (E) Low tidal volume (Low Vt) or high tidal volume (High Vt) ventilator treatment induced IL-6, IL-1β, and ICAM protein expression in the lung in WT mice. (F) NF-κB DNA binding activity of the lung was increased with the strength of ventilation in WT mice. NS=non-specific binding.

Decreased ventilator-induced lung damage in IKKβ^△mye mice. High tidal volume ventilation induced total number of cells in BALF (A), protein concentration in BALF (B), and pulmonary microvascular permeability (C) in WT mice but not in IKKβ^△mye mice. However, there was more neutrophil sequestration in the IKKβ^△mye mice (D). *P<0.05, **P<0.01, ***P<0.001. (E). E.coli. LPS stimulation-induced activation of alveolar macrophages was decreased in IKKβ^△mye mice when compared with WT mice.

Mechanical ventilation induced lung injury. The microvascular permeability was increased in ventilator treated WT mice as assayed with extravasation Evans Blue dye (A). The increased neutrophil infiltration (B) was demonstrated by increased myeloperoxidase (MPO) activity in the lung of WT mice with ventilator treatment. Total cell counts (C) and total protein concentration (D) in BALF were increased in WT mice with ventilator treatment. *P<0.05, **P<0.01, ***P<0.001. (E). The extent of neutrophil infiltration and alveolus swelling was observed in WT mice with low tidal volume (Low Vt) or high tidal volume (High Vt) ventilator treatment with HE stain.