interleukin-8 and Acidosis--Respiratory

Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-κB, a key transcriptional regulator in inflammation, injury, and repair.. Prospective randomized animal study.. University research laboratory.. Adult male Sprague-Dawley rats.. In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; FICO2 0.00) or (hypercapnic acidosis; FICO2 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-κB pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-κB pathway in hypercapnic acidosis-mediated protection from stretch injury was then determined.. Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-κB inhibitor IκBα and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-κB activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia.. Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-κB-dependent mechanism.

Topics: Acidosis, Respiratory; Animals; Biopsy, Needle; Blood Gas Analysis; Disease Models, Animal; Hemodynamics; Hypercapnia; Immunohistochemistry; Injury Severity Score; Interleukin-6; Interleukin-8; Male; NF-kappa B; Pulmonary Gas Exchange; Random Allocation; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; Survival Rate; Ventilator-Induced Lung Injury

It is known that carbon dioxide (CO2) pneumoperitoneum induces fetal acidosis in pregnant ewes. Our aim was to determine changes of the levels of maternal and fetal cytokines interleukin-6, interleukin-8, and tumor necrosis factor alpha after CO2 pneumoperitoneum in pregnant ewes. Eight ewes with singleton pregnancies of 120 to 140 days gestation were anesthetized and intubated. Insufflation produced modest but significant maternal arterial hypercapnia (an increase of 10.7 mm Hg; P<0.001) and acidosis (a decrease in mean pH of 0.1.04; P=0.0005). Fetal pCO2 was increased by 15.3 mm Hg on average and pH was decreased by 0.11 U on average immediately after desufflation (both P<0.001). No significant difference was observed in the concentration of cytokine in the maternal or fetal blood samples. These results suggest that respiratory acidosis does not lead to the elevation of cytokines in pregnant ewes and fetuses, which may contribute to premature labor.

Topics: Acidosis, Respiratory; Analysis of Variance; Animals; Carbon Dioxide; Cytokines; Female; Fetal Diseases; Fetus; Hypercapnia; Interleukin-6; Interleukin-8; Maternal-Fetal Exchange; Pneumoperitoneum, Artificial; Pregnancy; Risk Factors; Sheep; Time Factors; Tumor Necrosis Factor-alpha

Although permissive hypercapnia improves the prognosis of patients with acute respiratory distress syndrome, it has not been conclusively determined whether hypercapnic acidosis (HA) is harmful or beneficial to sustained inflammation of the lung. The present study was designed to explore the molecular mechanism of HA in modifying lipopolysaccharide (LPS)-associated signals in pulmonary endothelial cells. LPS elicited degradation of inhibitory protein kappaB (IkappaB)-alpha, but not IkappaB-beta, resulting in activation of nuclear factor (NF)-kappaB in human pulmonary artery endothelial cells. Exposure to HA significantly attenuated LPS-induced NF-kappaB activation through suppressing IkappaB-alpha degradation. Isocapnic acidosis and buffered hypercapnia showed qualitatively similar but quantitatively smaller effects. HA did not attenuate the LPS-enhanced activation of activator protein-1. Following the reduced NF-kappaB activation, HA suppressed the mRNA and protein levels of intercellular adhesion molecule-1 and interleukin-8, resulting in a decrease in both lactate dehydrogenase release into the medium and neutrophil adherence to LPS-activated human pulmonary artery endothelial cells. In contrast, HA did not inhibit LPS-enhanced neutrophil expression of integrin, Mac-1. Based on these findings, we concluded that hypercapnic acidosis would have anti-inflammatory effects essentially through a mechanism inhibiting NF-kappaB activation, leading to downregulation of intercellular adhesion molecule-1 and interleukin-8, which in turn inhibits neutrophil adherence to pulmonary endothelial cells.

Topics: Acidosis, Respiratory; CD11b Antigen; CD18 Antigens; Cell Adhesion; Cells, Cultured; Down-Regulation; Endothelium, Vascular; Endotoxins; Humans; Hypercapnia; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Interleukin-8; Lipopolysaccharides; Macrophage-1 Antigen; Neutrophils; NF-kappa B; Pulmonary Artery; Signal Transduction; Transcription Factor AP-1; Transcription Factors