Evidence of Abnormally Low Lymphocyte-To-Monocyte Ratio In COVID-19-Induced Severe Acute Respiratory Syndrome

2020 ◽  
Author(s):  
Paolo Lissoni
Keyword(s):  
Lung Injury ◽  
Respiratory Distress ◽  
Inflammatory Cytokines ◽  
Inflammatory Cells ◽  
Tnf Alpha ◽  
Control Group ◽  
Lymphocyte To Monocyte Ratio ◽  
System A ◽  
Infective Disease ◽  
Ventilator Therapy

It is known that lung injury due to COVID-19 responsible for the respiratory distress would mainly depend on host inflammatory response, depending on the excessive production of inflammatory cytokines, such as IL-6, and TNF-alpha, rather than direct virus-induced tissue damage, as well as for other forms of respiratory distress. Moreover, it is known that the inflammatory cytokines may induce profound changes in the behavior of the hematic cells, namely neutrophils, monocytes, and lymphocytes, with a following enhanced tissue infiltration by their inflammatory cells. According to the data available up to now, IL-6 and TNF-alpha would be the main cytokines involved in determining COVID-19-induced lung injury, as well as in other coronavirus infections, and most in general in all conditions of respiratory distress. Since it is known that the functionlessness of the whole immune system is namely depending on the interactions between lymphocyte and macrophage system, a preliminary study was planned to analyze the lymphocyte-to-monocyte ratio (LMR) in COVID-19 infective disease. The study included 17 consecutive patients, who underwent ventilator therapy for COVID-19-induced respiratory distress, and 100 healthy subjects, as a control group. Lymphocytopenia and monocytosis occurred in 14/17 (82%) and in 8/17(47%), respectively. Then, abnormally low values of LMR was found in 12/17 (71%) patients, and LMR men values observed in patients were significantly lower than in control (P<0.001). Therefore, by reflecting the interactions between lymphocyte and monocyte-macrophage systems, LMR could constitute a simple and less expensive biomarker to monitor the clinical evolution of COVID-19 infection.

scholarly journals HMGB1 and inflammatory cytokines in experimental acute lung injury induced in rabbits

2020 ◽  
Vol 72 (4) ◽  
pp. 1329-1338
Author(s):  
C.S. Kurokawa ◽  
J.P. Araújo Júnior ◽  
R.B. Pires ◽  
M.F. Carpi ◽  
M.A. Moraes ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
Tnf Alpha ◽  
Control Group ◽  
Early Expression

ABSTRACT The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.

scholarly journals Mesenchymal Stromal Cells Attenuate Infection-Induced Acute Respiratory Distress Syndrome in Animal Experiments: A Meta-Analysis

2020 ◽  
Vol 29 ◽  
pp. 096368972096918
Author(s):  
Wang Fengyun ◽  
Zhou LiXin ◽  
Qiang Xinhua ◽  
Fang Bin
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Meta Analysis ◽  
Weight Ratio ◽  
Lung Injury Score ◽  
Control Group ◽  
Inflammatory Factor

Mesenchymal stromal cell (MSC) therapy is a potential therapy for treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which was widely studied in the last decade. The purpose of our meta-analysis was to investigate the efficacy of MSCs for simulated infection-induced ALI/ARDS in animal trials. PubMed and EMBASE were searched to screen relevant preclinical trials with a prespecified search strategy. 57 studies met the inclusion criteria and were included in our study. Our meta-analysis showed that MSCs can reduce the lung injury score of ALI caused by lipopolysaccharide or bacteria (standardized mean difference (SMD) = −2.97, 95% CI [−3.64 to −2.30], P < 0.00001) and improve the animals’ survival (odds ratio = 3.64, 95% CI [2.55 to 5.19], P < 0.00001). Our study discovered that MSCs can reduce the wet weight to dry weight ratio of the lung (SMD = −2.58, 95% CI [−3.24 to −1.91], P < 0.00001). The proportion of the alveolar sac in the MSC group was higher than that in the control group (SMD = 1.68, 95% CI [1.22 to 2.13], P < 0.00001). Moreover, our study detected that MSCs can downregulate the levels of proinflammatory factors such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung and it can upregulate the level of anti-inflammatory factor IL-10. MSCs were also found to reduce the level of neutrophils and total protein in bronchoalveolar lavage fluid, decrease myeloperoxidase (MPO) activity in the lung, and improve lung compliance. MSC therapy may be a promising treatment for ALI/ARDS since it may mitigate the severity of lung injury, modulate the immune balance, and ameliorate the permeability of lung vessels in ALI/ARDS, thus facilitating lung regeneration and repair.

scholarly journals Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

2020 ◽  
Vol 19 (5) ◽  
pp. 1001-1007
Author(s):  
Qiong Hu ◽  
Chunai Yang ◽  
Fenshuang Zheng ◽  
Hongdan Duan ◽  
Yangshan Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Control Group ◽  
Western Blot Assay ◽  
Edema Formation ◽  
Sirt1 Expression ◽  
Treatment Groups

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury. Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1

Expression of p38 MAPK in Acute Lung Injury Induced by LPS in Mice

2014 ◽  
Vol 522-524 ◽  
pp. 332-336 ◽  
Author(s):  
Kai Xiu Qin ◽  
Yong Wang ◽  
Hua Gang Jian
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Inflammatory Cells ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Set Up

Objective To investigate the expression and roles of p38 mitogen-activated protein kinase (p38 MAPK) in LPS-induced acute lung injury (ALI) in mice. Methods The ALI mice models were set up by intraperineal injection of lipopolysaccharide (LPS). The expressions of p38 MAPK in lung tissues were detected by immunohistochemistry and Western-blot. Results The positive expressions of p38 MAPK distribute mainly in infiltrative inflammatory cells, epithelial cells and endothelial cells. And the level of expression of phosphated p38 MAPK in ALI group were higher obviously than that in the control group, and it reached a peak after two hours. Conclusion p38 MAPK signaling pathway was triggered by ALI induced by endotoxin.

Roflumilast, a phosphodiesterase-4 inhibitor, improves hyperoxia-induced lung injury via anti-inflammation

2020 ◽  
Vol 47 (2) ◽  
pp. 189-196
Author(s):  
Hong-Ying Cao ◽  
◽  
Tian-Hua Yu ◽  
Cui-Hong Han ◽  
Wen-Wu Liu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Pure Oxygen ◽  
Control Group ◽  
Lung Edema ◽  
Lung Pathology ◽  
Protective Effects ◽  
Lactate Dehydrogenase Activity ◽  
Phosphodiesterase 4 ◽  
Hyperoxia Exposure

Roflumilast is an inhibitor of phosphodiesterase-4 (PDE4) and can suppress the hydrolysis of cAMP in inflammatory cells, conferring anti-inflammatory effects. This study aimed to investigate the protective effects of roflumilast on hyperoxia-induced acute lung injury (HALI) in a rat model. Male Sprague-Dawley rats were randomly assigned into: control group; HALI group; 2.5 mg/kg roflumilast group; and 5 mg/kg roflumilast group. Rats were pressurized to 250 kPa with pure oxygen to induce lung injury. In the roflumilast groups, rats were orally administered with roflumilast at 2.5 or 5 mg/kg once before hyperoxia exposure and once daily for two days after exposure. Rats were sacrificed 72 hours after hyperoxia exposure. The lung tissues were collected for the detection of lung water content, inflammatory cytokines and NF-κB/p-NF-κB protein expression, and the bronchoalveolar lavage fluid was harvested for the measurement of protein concentration and lactate dehydrogenase activity. Results showed roflumilast at different doses could significantly reduce lung edema, improve lung pathology and reduce the expression of inflammatory cytokines in the lung. The protective effects seemed to be related to the dose of roflumilast. Our study indicates roflumilast has the potential as a medication for the treatment of HALI.

scholarly journals The Activation of Macrophage and Upregulation of CD40 Costimulatory Molecule in Lipopolysaccharide-Induced Acute Lung Injury

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Liang Dong ◽  
Shujuan Wang ◽  
Ming Chen ◽  
Hongjia Li ◽  
Wenxiang Bi
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Costimulatory Molecule ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Vital Role ◽  
Control Group ◽  
Toll Like Receptor 4 ◽  
Activated Macrophage ◽  
Lps Treatment

To study the activation of macrophage and upregulation of costimulatory molecule of CD40 in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) model, and to investigate the pathogenecy of ALI, mice were randomly divided into two groups. ALI model was created by injecting 0.2 mg/kg LPS in phosphate saline (PBS) in trachea. The pathologic changes of mice lungs were observed by HE staining at 24 and 48 hours after LPS treatment, then the alveolar septum damage, abnormal contraction, alveolar space hyperemia, and neutrophils or other inflammatory cells infiltration in the LPS group, but not in the control group, were observed. The expression of CD40 mRNA and CD40 protein molecules were higher in LPS group as compared to the control group by Northern blot and flow cytometry, respectively. Expression of Toll-like receptor-4 (TLR4) in activated macrophage (AM) was higher in LPS group as compared to the control group by RT-PCR. The activation of NF-B binding to NF-B consensus oligos increased in LPS group by EMSA in macrophage. The concentrations of TNF-, MIP-2, and IL-1 cytokines from bronchoalveolar lavage fluid (BALF) were increased significantly in LPS group as compared to the control group by ELISA. The activation of AM and upregulation of costimulatory molecule CD40 induced all kinds of inflammatory cytokines releasing, then led to ALI. Therefore, both of them played vital role in the process of development of ALI.

scholarly journals Level of pro-inflammatory cytokines in patients with transfusion-related acute lung injury - Multiple comparisons between patients, controls and donor

2019 ◽  
Vol 10 (2) ◽  
pp. 1448-1455
Author(s):  
Adil Shaker Al-Tamimi ◽  
Israa A. Dheeb
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Case Control Study ◽  
Serum Levels ◽  
Tnf Alpha ◽  
Blood Component ◽  
Ventilator Support ◽  
Control Study ◽  
Pro Inflammatory Cytokines

Transfusion-related acute lung injury recently regarded as the leading cause of death after transfusion. Several pro-inflammatory cytokines TNF, IL6 and IL8 have been linked to the pathogenesis of TRALI, supported by the findings of increased their serum levels in recipient patients. This is a prospective case-control study, twenty-five patients with a diagnosis of TRALI after transfusion of blood products were included and compared to another 25 transfused patients. Serum was obtained after the onset of TRALI in patients and controls. Other samples were obtained from the saved donor transfused bag or segments. All samples were utilized for cytokines assay. The intubation rate among TRALI patients was 48%. No difference was found in the regarding the type of transfusion and the cytokine level for each specific type of blood or blood component transfused between TRALI and controls. The overall TRALI associated mortality was 4%. Results revealed significantly increased TNF alpha IL-6 levels in sera of TRALI patients as compared with control and donor unit for patients with TRALI. Serum levels of IL-8 were significantly higher in patients with TRALI (mean42.11 pg/ml) as compared with sera of control and donor unit for TRALI patients. Serum level of TNF, IL-6 and-8 in patients with TRALI was significantly higher in patients with longer incubation time. Serum cytokines assay in patients with TRALI may add the significant advantage of assessing the severity, associated mortality and predicting the time of ventilator support.

scholarly journals Alleviation of Lipopolysaccharides-Induced Acute Lung Injury by MiR-454

2016 ◽  
Vol 38 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Zhengang Tao ◽  
Ying Yuan ◽  
Qingwu Liao
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Inflammatory Cells ◽  
Protein Translation ◽  
Luciferase Reporter ◽  
Mouse Lung ◽  
Common Disease ◽  
Permeability Index ◽  
Promising Therapeutic Approach

Background/Aims: Although acute lung injury (ALI) is an important and common disease in humans, its pathogenesis is poorly understood and its therapeutic outcome has not been significantly improved in the past years. Here, we examined whether application of microRNAs might inhibit the ALI-associated lung inflammatory, and subsequently reduce the injury. Methods: In vitro, we performed bioinformatics analyses to identify the miRNAs that target the most important chemo-attractive factor CXCL12, and confirmed that the binding was functional by luciferase reporter assay. We prepared adeno-associated virus (AAV) carrying miRNA mimics or null control. We expressed miRNA in mouse lung through i.v. injection of AAV and then we used Lipopolysaccharides (LPS) to induce ALI in mice. We analyzed the changes in permeability index and production of inflammatory cytokines in mouse lung, and we also verified the effects of virus-mediated gene expression by examining the levels of miRNAs and CXCL12 in lung by RT-qPCR and ELISA, and by quantifying the recruited inflammatory cells in mouse lung by flow cytometry. Results: We found that miR-454 targeted the 3'-UTR of CXCL12 mRNA to inhibit its protein translation in human lung epithelial cells. Overexpression of miR-454 in mouse lung significantly reduced the LPS-induced increases in permeability index and production of inflammatory cytokines CXCL1, CXCL2, IL6 and TNFα, possibly through suppression of CXCL12/CXCR4-mediated recruitment of inflammatory cells. Conclusion: Overexpression of miR-454 in lung may be a promising therapeutic approach to reduce the severity of ALI.

scholarly journals The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?

2016 ◽  
Vol 311 (3) ◽  
pp. L639-L652 ◽  
Author(s):  
Andreas Schwingshackl
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Ion Channels ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Oxygen Toxicity ◽  
Inflammatory Cells ◽  
Future Research ◽  
Stretch Activated Ion Channels

Mechanical ventilation (MV) and oxygen therapy (hyperoxia; HO) comprise the cornerstones of life-saving interventions for patients with acute respiratory distress syndrome (ARDS). Unfortunately, the side effects of MV and HO include exacerbation of lung injury by barotrauma, volutrauma, and propagation of lung inflammation. Despite significant improvements in ventilator technologies and a heightened awareness of oxygen toxicity, besides low tidal volume ventilation few if any medical interventions have improved ARDS outcomes over the past two decades. We are lacking a comprehensive understanding of mechanotransduction processes in the healthy lung and know little about the interactions between simultaneously activated stretch-, HO-, and cytokine-induced signaling cascades in ARDS. Nevertheless, as we are unraveling these mechanisms we are gathering increasing evidence for the importance of stretch-activated ion channels (SACs) in the activation of lung-resident and inflammatory cells. In addition to the discovery of new SAC families in the lung, e.g., two-pore domain potassium channels, we are increasingly assigning mechanosensing properties to already known Na+, Ca2+, K+, and Cl− channels. Better insights into the mechanotransduction mechanisms of SACs will improve our understanding of the pathways leading to ventilator-induced lung injury and lead to much needed novel therapeutic approaches against ARDS by specifically targeting SACs. This review 1) summarizes the reasons why the time has come to seriously consider SACs as new therapeutic targets against ARDS, 2) critically analyzes the physiological and experimental factors that currently limit our knowledge about SACs, and 3) outlines the most important questions future research studies need to address.

scholarly journals Protective Effect of Quercetin, a Flavonol against Benzo(a)pyrene-Induced Lung Injury via Inflammation, Oxidative Stress, Angiogenesis and Cyclooxygenase-2 Signalling Molecule

2021 ◽  
Vol 11 (18) ◽  
pp. 8675
Author(s):  
Mohammad A. Alzohairy ◽  
Amjad Ali Khan ◽  
Mohammad Azam Ansari ◽  
Ali Yousif Babiker ◽  
Mohammed A. Alsahli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Treatment Group ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Cyclooxygenase 2 ◽  
Inflammatory Factors ◽  
Control Group ◽  
Cox 2

Quercetin (Qu) is an important polyphenolic flavonoid which exhibits tremendous antioxidant, anti-inflammatory and other health promoting effects. The aim of the current study was to explore the therapeutic role of Qu on benzo(a)pyrene [B(a)P]-induced lung injury in rats. B(a)P was given to the rats at dose of 50 mg/kg b.w. for continues 8 weeks through oral gavage. The rats were treated with Qu at dose of 50 mg/kg b.w prior 30 min before the oral administration of B(a)P. The effects of Qu were studied by measuring the level of lactate dehydrogenase (LDH), anti-oxidant enzymes, lipid peroxidation, inflammatory cytokines, lung tissues architecture and expression of cyclooxygenase-2 (COX-2). The level of pro‑inflammatory cytokines such as IL-1β (27.30 vs. 22.80 pg/mL), IL-6 (90.64 vs. 55.49 pg/mL) and TNF-α (56.64 vs. 40.49 pg/mL) increased significantly and antioxidant enzymes decreased significantly in benzopyrene-induced lung injury in comparison to the control group. The treatment with Qu potentially reversed the effects of B(a)P to a great extent, as it led to the enhancement of antioxidant enzymes and decreased proinflammatory cytokines level. A significant surge of VEGF level was noticed in the B(a)P group as compared to the control group, while the Qu treatment groups exhibited less angiogenesis as lower level of VEGF levels, compared with the B(a)P treatment group. The Qu treatment significantly decreased the degrees of histopathological changes and collagen deposition in B(a)P-induced lung injury. The B(a)P-treated group showed higher cytoplasmic expression of COX-2 protein, which significantly decreased in the Qu treatment group. These outcomes recommend an effective role of Qu in the protection of lung injury against B(a)P through the regulation of the inflammatory factors, oxidative stress and the maintenance lung tissue architecture.

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