No abstract

Rationale-Apocynin suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesized that apocynin attenuates VILI.Methods-VILI was induced by mechanical ventilation with tidal volume (V t ) of 15 ml/kg in isolated and perfused rat lung. Apocynin was administered in the perfusate at onset of mechanical ventilation. A group ventilated with low V t of 5 ml/kg served as control. Hemodynamics, lung Results-There was an increase in lung permeability and lung weight gain after mechanical ventilation with high V t , compared with low V t . Levels of inflammatory cytokines including interleukin-1b (IL-1b), tumor necrosis factor-alpha (TNF-a), and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; concentrations of carbonyl, thiobarbituric acid reactive substances, and H 2 O 2 were higher in perfusates and lung lavage fluids, and expression of myeloperoxidase, JNK, p38, and caspase-3 in lung tissue was greater in the high-Vt than in the low-Vt group. Administration of apocynin attenuated these inflammatory responses and lung permeability associated with decreased activation of nuclear factor-κB.Conclusions-VILI is associated with inflammatory responses including generation of ROS, cytokines, and activation of mitogen-activated protein kinase cascades. Administration of apocynin at onset of mechanical ventilation attenuates inflammatory responses and VILI in the isolated, perfused rat lung model.

No abstract

The genetic polymorphism of the TNF-α is associated with COPD. Both TGF-β1 and TNF-α modulate clinical severity and airflow limitation in an additive manner.

BACKGROUND: The role of transforming growth factor ␤1 (TGF-␤1) and tumor necrosis factor ␣ (TNF-␣) in asthma is unclear. The aim of this study was to assess the relationships among polymorphisms, clinical phenotypes, and the serum levels of TGF-␤1 and TNF-␣. METHODS: Polymorphisms of promoter of TGF-␤1 (C-509T locus) and TNF-␣ (G-308 A locus; rs 1800629) in 217 asthmatic patients and 110 healthy controls were evaluated. Pulmonary function, total immunoglobulin E (IgE), specific IgE antibodies, total eosinophil counts, TGF-␤1, and TNF-␣ were assessed. RESULTS: The genetic polymorphisms of TGF-␤1 promoter and TNF-␣ were significantly associated with asthma. Subjects with more severe asthma had higher serum levels of TGF-␤1 and TNF-␣. In asthmatic subjects the TGF-␤1 of atopic subjects was higher than those without atopy. All studied subjects (asthma plus control) were divided into 4 groups by mean value of TGF-␤1 or TNF-␣. The high values of TGF-␤1 or TNF-␣ were defined by higher than the mean values of the studied subjects of TGF-␤1 (392.42 pg/mL) and TNF-␣ (55.86 pg/mL). The FEV 1 of the group with high TGF-␤1 plus low TNF-␣ was lower than that in the group with low TGF-␤1 plus low TNF-␣. The lowest FEV 1 was in the group with high TNF-␣ and high TGF-␤1. CONCLUSIONS: The genetic polymorphisms of TGF-␤1 and TNF-␣ are associated with asthma. TGF-␤1 modulates atopy. Both TGF-␤1 and TNF-␣ modulate clinical severity and airway obstruction, in an additive manner.