scholarly journals C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

2008 ◽  
Vol 180 (11) ◽  
pp. 7368-7375 ◽  
Author(s):  
Konstantinos Kambas ◽  
Maciej M. Markiewski ◽  
Ioannis A. Pneumatikos ◽  
Stavros S. Rafail ◽  
Vassiliki Theodorou ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Tissue Factor ◽  
Distress Syndrome ◽  
Tnf Α

scholarly journals Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 431
Author(s):  
Matthias Otto ◽  
Jörg Krebs ◽  
Peter Welker ◽  
René Holm ◽  
Manfred Thiel ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Lung Mechanics ◽  
Systemic Absorption ◽  
Control Group ◽  
Pharmacokinetic Data ◽  
Tnf Α ◽  
Semifluorinated Alkanes

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

scholarly journals Silencing of long noncoding RNA H19 alleviates pulmonary injury, inflammation and fibrosis in acute respiratory distress syndrome rats through regulating MicroRNA-423-5p

2020 ◽  
Author(s):  
Xianyu Mu ◽  
Hongrong Wang ◽  
Haiyong Li
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Distress Syndrome ◽  
Luciferase Reporter ◽  
Pulmonary Injury ◽  
Tnf Α ◽  
Histology Score

Abstract Background: This study aimed to explore the function of long noncoding RNA H19 (H19) on pulmonary injury, inflammation and fibrosis in lipoproteins (LPS)-induced acute respiratory distress syndrome (ARDS) rats. Methods: The LPS-induced ARDS rat model was established by intratracheal instillation with 2 mg/kg LPS. QRT-PCR was performed to detect the expression of H19, miR-423-5p, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6,, monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF). Histology score was detected by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of proinflammatory cytokines and the concentration of VEGF in bronchoalveolar lavage fluid (BALF). The protein expression of fiber factors was measured by western blot. The degree of fibrosis was observed by masson-trichrome staining. Dual-luciferase reporter assay was used to determine the binding site between miR-423-5p and H19.Results: The expression of H19 was significantly increased, while miR-423-5p was decreased in LPS-induced ARDS rats. Silencing of H19 decreased the mRNA expression of TNF-α, IL-1β, IL-6, MCP-1 and VEGF in LPS-induced ARDS rats, and decreased the levels of TNF-α, IL-1β, IL-6and the concentration of VEGF in BALF, histology score of LPS-induced ARDS rats. H19 inhibition also decreased the fibrosis score and the proteins expression of fiber factors of LPS-induced ARDS rats. Furthermore, miR-423-5p eliminated the effect of H19 on LPS-induced MH-S cells.Conclusions: Silencing of H19 ameliorated the pulmonary injury, inflammation and fibrosis of LPS-induced ARDS through regulating miR-423-5p, which may be a promising therapeutic strategy to treat ARDS.

scholarly journals Diagnostic value of miR-155 for acute lung injury/acute respiratory distress syndrome in patients with sepsis

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094307
Author(s):  
Zhou-Feng Wang ◽  
Yu-Min Yang ◽  
Heng Fan
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Inflammatory Factors ◽  
Tnf Α

Objective We aimed to investigate the diagnostic value of microRNA-155 (miR-155) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) in patients with sepsis. Methods In this prospective study, we used Spearman correlation analysis to investigate relationships between miR-155 expression and inflammatory factors, oxygenation ratio (PaO2/FiO2), and ALI/ARDS score, and used area under the receiver operating characteristic curve (AU-ROC) to evaluate miR-155's diagnostic accuracy for ALI/ARDS in patients with sepsis. Results In total, 156 patients with sepsis were enrolled in our study, of which 41 had ALI and 32 had ARDS. miR-155 expression in plasma of patients with sepsis and ALI/ARDS was significantly higher than that of patients with sepsis but no ALI/ARDS. The miR-155 level in patients with sepsis and ALI/ARDS was positively correlated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels and ALI/ARDS score, but negatively correlated with PaO2/FiO2. The AU-ROC of plasma miR-155 for diagnosis of sepsis with ALI/ARDS was 0.87, and plasma miR-155, IL-1β, and TNF-α had high sensitivity and specificity for the diagnosis of sepsis with ALI/ARDS. Conclusion miR-155 is highly expressed in plasma of patients with septic ALI/ARDS; it is positively correlated with lung function and can be used for early diagnosis.

scholarly journals Effects of Tocilizumab, an Interleukin-6 Receptor Antagonist, on Cytokine Expression and Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome

Biomeditsina ◽  
2020 ◽  
Vol 16 (4) ◽  
pp. 60-70
Author(s):  
V. N. Karkischenko ◽  
I. A. Pomytkin ◽  
N. V. Petrova ◽  
S. V. Maksimenko ◽  
M. M. Skripkina ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Interleukin 6 ◽  
Distress Syndrome ◽  
Cytokine Expression ◽  
Animal Survival ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Receptor Signaling Pathway

This study aims to investigate effects of tocilizumab, a monoclonal antibody to interleukin-6 (IL-6) receptors, on cytokine expression and animal survival in a model of fatal acute respiratory distress syndrome (ARDS) characterized by high mortality rates and increased IL-6 production in the lungs. The expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor (TNF-α) and interferons α (IFN-α) and β (IFN-β) in the lungs was assessed by real-time PCR. Cytokine production was assessed by enzyme immunoassay. Although tocilizumab did not affect the expression of the studied cytokines in the lungs of animals with ARDS, it changed the profiles of their release. An acute multifold increase in the levels of IL-6 in the lungs was observed in the first two hours after the administration of tocilizumab, followed by a decrease of IL-6 to lower values similar to those observed in intact animals. Tocilizumab did not reduce mortality in treated animals with ARDS compared to those without treatment. Thus, the inhibition of the IL-6 receptor signaling pathway alone does not provide an effective solution to the problem of reducing mortality from ARDS associated with the development of a “cytokine storm”.

scholarly journals Assessment of a Novel Method for Non-invasive Sampling of the Distal Airspace in Acute Respiratory Distress Syndrome Patients Receiving Inhaled Sedation with Sevoflurane: the ANAISS Study Protocol

2020 ◽  
Author(s):  
Pierre-Antoine Tronche ◽  
Robin Lalande ◽  
Raiko Blondonnet ◽  
Laurence Roszyk ◽  
Ruoyang Zhai ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Pulmonary Oedema ◽  
Study Protocol ◽  
Distress Syndrome ◽  
Non Invasive ◽  
Tnf Α ◽  
Distal Airspace ◽  
Oedema Fluid

ABSTRACTIntroductionRecently, fluid collected from the heat-and-moisture-exchange filters, which are commonly used in most mechanically ventilated patients under intravenous sedation, has been reported as a potential surrogate for fluid in the distal airspace. Therefore, collection of this fluid represents a promising, non-invasive method for sampling the distal airspace in patients with acute respiratory distress syndrome (ARDS) and for facilitating a mechanistic understanding of this devastating disease. The current study protocol was constructed to assess whether this fluid could be sampled from a dedicated device (Anaesthetic Conserving Device [AnaConDa-S], Sedana Medical, Danderyd, Sweden) used to deliver inhaled sevoflurane for sedation in patients with ARDS.Methods and analysisA total of 30 adult patients within 24 hours of meeting the Berlin criteria for moderate-severe ARDS and receiving inhaled sevoflurane as standard sedation in participating centres will be eligible for inclusion into this investigator-initiated, exploratory, prospective, bicentre study. After at least 12 h of inhaled sedation, a sample of directly aspirated, undiluted pulmonary oedema fluid will be collected concurrently with fluid from the AnaConDa-S device. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α and sTNFr-1) and markers of lung endothelial (Ang-2) and epithelial (sRAGE) injury will be measured in both fluids by Multiplex. The primary endpoint is the correlation between protein markers (IL-1β, IL-6, IL-8, TNF-α, sTNFr-1, Ang-2 and sRAGE) measured in the undiluted pulmonary oedema fluid versus the AnaConDa-S fluid.Ethics and disseminationThe study was approved by the appropriate ethics committee (CPP Est I). Informed consent is required. The fluid collection from the AnaConDa-S has potential to foster our understanding of the potential effects of inhaled sedation in clinical ARDS and to open up novel perspectives for prognostic and predictive enrichment in future trials. The results will be published in a peer-reviewed journal.Registration numberNCT03964155.

scholarly journals Autotaxin levels in serum and bronchoalveolar lavage fluid are associated with inflammatory and fibrotic biomarkers and the clinical outcome in patients with acute respiratory distress syndrome

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lijuan Gao ◽  
Xiaoou Li ◽  
Hao Wang ◽  
Yue Liao ◽  
Yongfang Zhou ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Bronchoalveolar Lavage ◽  
Sofa Score ◽  
Bronchoalveolar Lavage Fluid ◽  
Distress Syndrome ◽  
Lavage Fluid ◽  
Apache Ii Score ◽  
Tnf Α

Abstract Background Autotaxin (ATX) is a secreted glycoprotein that is widely present in extracellular biological fluids and has been implicated in many inflammatory and fibrotic diseases. However, the clinical impact of the release of ATX in patients with acute respiratory distress syndrome (ARDS) remains unclear. Methods Serum and bronchoalveolar lavage fluid (BALF) levels of ATX, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-7, fibronectin, oncostatin M (OSM), and SPARC (secreted protein acidic and rich in cysteine) were collected from 52 patients with ARDS within 24 h of diagnosis. All cytokines were measured by Magnetic Luminex Assay. BALF albumin (BA) and serum albumin (SA) were measured by enzyme-linked immunosorbent assay. Results Serum ATX, MMP-7, and BALF IL-8 levels were significantly higher in patients who did not survive than in those who survived up to 28 days after diagnosis of ARDS (P < 0.05). BALF and serum ATX levels were correlated with IL-6, IL-8, and MMP-7 levels in BALF and serum, respectively. In addition, BALF ATX was positively correlated with BALF TNF-α, fibronectin, OSM, and SPARC as well as the BA/SA ratio, while serum ATX was correlated with severity of illness based on the SOFA score and PaO2/FIO2 ratio. Furthermore, serum ATX was better able to predict 28-day ARDS-related mortality (area under the curve 0.744, P < 0.01) than the SOFA score, APACHE II score, or PaO2/FIO2 ratio. Serum ATX independently predicted mortality in a univariate Cox regression model (P < 0.0001). Conclusion The serum ATX level is a potential prognostic biomarker in patients with ARDS. BALF ATX is associated with pulmonary biomarkers of inflammation and fibrosis, suggesting a role of ATX in the pathogenesis of ARDS.

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