interleukin-8 and Hypercapnia

Congenital heart disease (CHD) after cardiopulmonary bypass can cause systemic inflammation, and its degree is closely related to the incidence of acute respiratory distress syndrome (ARDS). The purpose of this study was to determine the effectiveness of high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG) in reducing systemic inflammation in infants with ARDS after cardiopulmonary bypass for congenital heart surgery.. A randomized controlled trial.. Single-center study in a tertiary teaching hospital.. A total of 58 infants with ARDS after congenital heart surgery were eligible and were randomized to the HFOV (n = 29) or the HFOV-VG (n = 29) between January 2020 and January 2021.. Tracheal aspirate samples for the measurement of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were obtained on days one, two, and three of HFOV or HFOV-VG ventilation.. The authors found a significantly increasing trend in the HFOV group mean values of IL-6, IL-8, and TNF-α (p < 0.05 on days two and three v day one), and IL-6, IL-8, and TNF-α levels were significantly higher on day three in the HFOV group versus the HFOV+VG group (p < 0.05). In addition, the incidences of hypocapnia and hypercapnia in infants supported with HFOV-VG were significantly lower (p < 0.05). Furthermore, the postoperative mechanical ventilation duration in the HFOV-VG group also was shorter than that in the HFOV group (p < 0.05).. Compared with HFOV alone, HFOV-VG reduced proinflammatory systemic reactions after congenital cardiac surgery, decreased the incidences of hypercapnia and hypocapnia, and shortened the postoperative mechanical ventilation duration.

Topics: High-Frequency Ventilation; Humans; Hypercapnia; Hypocapnia; Infant; Infant, Newborn; Infant, Premature; Inflammation; Interleukin-6; Interleukin-8; Lung; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha

Tidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration.. Twenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined.. There were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups.. This open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted.. ACTRN12607000465459.

Topics: Aged; Female; Humans; Hypercapnia; Interleukin-8; Lung Compliance; Male; Middle Aged; Oxygen; Pilot Projects; Positive-Pressure Respiration; Pressure; Respiratory Distress Syndrome; Tidal Volume; Treatment Outcome; Tumor Necrosis Factor-alpha

To investigate the role of vagus nerve activation in the protective effects of hypercapnia in ventilator-induced lung injury (VILI) rats.. Male Sprague-Dawley rats were randomized to either high-tidal volume or low-tidal volume ventilation (control) and monitored for 4h. The high-tidal volume group was further divided into either a vagotomy or sham-operated group and each surgery group was further divided into two subgroups: normocapnia and hypercapnia. Injuries were assessed hourly through hemodynamics, respiratory mechanics and gas exchange. Protein concentration, cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight and pathological changes were examined. Vagus nerve activity was recorded for 1h.. Compared to the control group, injurious ventilation resulted in a decrease in PaO2/FiO2 and greater lung static compliance, MPO activity, enhanced BALF cytokines, protein concentration, cell count, and histology injury score. Conversely, hypercapnia significantly improved VILI by decreasing the above injury parameters. However, vagotomy abolished the protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced efferent vagus nerve activity compared to normocapnia.. These results indicate that the vagus nerve plays an important role in mediating the anti-inflammatory effect of hypercapnia on VILI.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Hypercapnia; Interleukin-8; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Vagotomy; Vagus Nerve; Ventilator-Induced Lung Injury

Patients with Acute Hypercapnic Respiratory Failure (AHRF) who are unresponsive to appropriate medical treatment, are often treated with Noninvasive Positive Pressure Ventilation (NPPV). Clinical predictors of the outcome of this treatment are scarce. Therefore, we evaluated the role of the biomarkers IL-8 and GDF-15 in predicting 28-day mortality in patients with AHRF who receive treatment with NPPV.. The study population were 46 patients treated with NPPV for AHRF. Clinical and background data was registered and blood samples taken for analysis of inflammatory biomarkers. IL-8 and GDF-15 were selected for analysis, and related to risk of 28-day mortality (primary endpoint) using Cox proportional hazard models adjusted for gender, age and various clinical parameters.. Of the 46 patients, there were 3 subgroup in regards to primary diagnosis: Acute Exacerbation of COPD (AECOPD, n = 34), Acute Heart Failure (AHF, n = 8) and Acute Exacerbation in Obesity Hypoventilation Syndrome (AEOHS, n = 4). There was significant difference in the basic characteristic of the subgroups, but not in the clinical parameters that were used in treatment decisions. 13 patients died within 28 days of admission (28%). The Hazard Ratio for 28-days mortality per 1-SD increment of IL-8 was 3.88 (95% CI 1.86-8.06, p < 0.001). When IL-8 values were divided into tertiles, the highest tertile had a significant association with 28 days mortality, HR 10.02 (95% CI 1.24-80.77, p for trend 0.03), compared with the lowest tertile. This correlation was maintained when the largest subgroup with AECOPD was analyzed. GDF-15 was correlated in the same way, but when put into the same model as IL-8, the significance disappeared.. IL-8 is a target to explore further as a predictor of 28 days mortality, in patients with AHRF treated with NPPV.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Female; Growth Differentiation Factor 15; Humans; Hypercapnia; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Noninvasive Ventilation; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Sweden

Hypercapnia is known to have immunoregulatory effects within the lung. Cell culture systems demonstrate this in both macrophages and alveolar cell lines, suggesting that the alveoli are affected by changes in CO2 levels. We hypothesized that hypercapnia would also modulate human bronchial epithelial cell immune responses. Innate immune responses to Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand) and a complex innate immune stimulus, an extract from the organic dust of swine confinement barns (barn dust extract or BDE), were tested in a human bronchial epithelial cell line, BEAS-2B. Both TLR ligands showed a decrease in IL-6 and IL-8 production, and an increase in MCP-1 in response to elevated CO2 indicating an enhancement in cytokine production to hypercapnia. This change was not reflected in expression levels of TLR receptor RNA which remained unchanged in response to elevated CO2. Interestingly, barn dust showed an increase in IL-6, IL-8 and MCP-1 response at 9% CO2, suggesting that elevated CO2 exerts different effects on different stimuli. Our results show that airway epithelial cell immune responses to barn dust respond differently to hypercapnic conditions than individual TLR ligands.

Topics: Air Pollution, Indoor; Animals; Bronchi; Carbon Dioxide; Cell Line; Chemokine CCL2; Dust; Hypercapnia; Immunity, Innate; Inflammation Mediators; Interleukin-8; Lipopeptides; Lipopolysaccharides; Respiratory Mucosa; Swine; Toll-Like Receptor 2; Toll-Like Receptor 4

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

Reducing tidal volume as a part of a protective ventilation strategy may result in hypercapnia. In this study, we focused on the influence of hypercapnia on endothelial-neutrophil responses in models of inflammatory-stimulated human pulmonary microvascular endothelial cells (HMVEC) and in an animal model of lipopolysaccharide (LPS)-induced acute lung injury. Neutrophil adhesion and adhesion molecules expression and nuclear factor-kappaB (NF-kappaB) were analyzed in TNF-alpha and LPS-treated HMVEC exposed to either eucapnia or hypercapnia. In the in vivo limb, bronchoalveolar lavage fluid cell counts and differentials, adhesion molecule and chemokine expression were assessed in LPS-treated rabbits ventilated with either low tidal volume ventilation and eucapnia or hypercapnia. In both the in vitro and in vivo models, hypercapnia significantly increased neutrophil adhesion and adhesion molecule expression compared to eucapnia. Activity of NF-kappaB was significantly enhanced by hypercapnia in the in vitro experiments. IL-8 expression was greatest both in vitro and in vivo under conditions of hypercapnia and concomitant inflammation. CD11a expression was greatest in isolated human neutrophils exposed to hypercapnia+LPS. Our results demonstrate that endothelial-neutrophil responses per measurement of fundamental molecules of adhesion are significantly increased during hypercapnia and that hypercapnia mimics conditions of eucapnia+inflammation.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; E-Selectin; Endothelial Cells; Endothelium, Vascular; Humans; Hypercapnia; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Lipopolysaccharides; Neutrophils; P-Selectin; Rabbits; Vascular Cell Adhesion Molecule-1

To explore the protective effects of hypercapnia on acute lung injury (ALI) and the possible mechanisms.. Twenty-four healthy New Zealand white rabbits were involved in this study, and randomly divided to three groups, a control group, a therapeutic group, and a prophylactic group (n=8, each). Lipopolysaccharide (1 mg/kg) was injected intravenously to establish the ALI model. Blood gas analysis and artery pressure were monitored. IL-8 and TNF-alpha in the serum and bronchoalveolar lavage fluid (BALF), wet weight/dry weigh (W/D), index of quantitative assessment of histological lung injury (IQA), myeloperoxidase (MPO) and malondialdehyde (MDA) activity in the lung tissue were measured. Apoptosis index of neutrophils were determined.. (1) The mean artery pressure, heart rate, PaCO2, and PaO2/FiO2 changed in the ALI model of the therapeutic group and the prophylactic group [(79+/-6) mm Hg (1 mm Hg=0.133 kPa), (180+/-10)/min, (99+/-13) mm Hg, 250+/-26, (80+/-9) mm Hg, (181+/-12)/min, (95+/-11) mm Hg, 241+/-56, respectively]. In the control group, they were (66+/-10) mm Hg, (139+/-13)/min, (31+/-4) mm Hg, 182+/-35, respectively. The differences were significant compared with the control group (t=4.05, 26.32, 5.36, 28.15, 12.54, 11.07, 16.13, 12.36, P<0.05, 0.01). (2) The levels of W/D, MPO, and MDA in the therapeutic group and the prophylactic group were 1.98+/-0.28, 1.87+/-0.30, (6.1+/-1.6) U/g, (5.8+/-1.5) U/g, (20+/-5) mg/L, (19+/-4) mg/L; while in the control group, they were [2.43+/-0.26, (9.0+/-1.3) U/g, (36+/-8) mg/L] respectively. The difference was significant (t=11.07, 24.46, 2.35, 9.63, 12.34, 25.32, P<0.05, 0.01). (3) The levels of IL-8 and TNF-alpha in the serum and BALF and the apoptosis index in the three groups were (50+/-8) ng/ml, (103+/-49) ng/ml, (94+/-16) ng/ml, (44+/-9) ng/ml, (38+/-9)%, (56+/-5)%, (49+/-7) ng/ml, (96+/-50) ng/ml, (91+/-14) ng/ml, (39+/-6) ng/ml, (39+/-10)%, (55+/-10)%, (91+/-43) ng/ml, (177+/-60) ng/ml, (162+/-15) ng/ml, (67+/-7) ng/ml, (19+/-7)%, (43+/-7)%, respectively. The difference was significant among the three groups (t=7.12, 5.55, 7.30, 3.93, 13.08, 8.00, P<0.05, 0.01 respectively). (4) The apoptosis index of neutrophils was negatively correlated with the levels of IL-8 in the serum and BALF (r=-0.73, -0.72, -0.52, -0.64, -0.73, -0.56, all P<0.05), and the levels of TNF-alpha in the serum and BALF (r=-0.57, -0.78, -0.69, -0.75, -0.82, -0.84, all P<0.05).. Hypercapnia does not affect hemodynamics and has protective effects on ALI.

Topics: Acute Lung Injury; Animals; Apoptosis; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Hemodynamics; Hypercapnia; Interleukin-8; Lipopolysaccharides; Lung; Male; Malondialdehyde; Peroxidase; Rabbits; Random Allocation; Respiratory Function Tests; Tidal Volume

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