The features of the course of virus-associated acute lung injury in mice with induced immunosuppression

2021 ◽  
Vol 21 (3) ◽  
pp. 75-80
Author(s):  
Andrey G. Aleksandrov
Keyword(s):  
Influenza Virus ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Influenza Infection ◽  
Lung Damage ◽  
Experimental Therapy ◽  
Blood Oxygen ◽  
Blood Oxygen Saturation ◽  
Pro Inflammatory Cytokines

BACKGROUND: Among all groups of patients with virus-associated acute lung injury with influenza infection, the most severe course is observed in patients with immunosuppression. In this case, despite the studied mechanism of the course of combined pathology, the question of therapy in this group of patients remains unclear. AIM: To study the features of the course of acute lung injury in influenza infection with secondary immunosuppression in an experiment for the possibility of searching for experimental therapy for this combined pathology. MATERIALS AND METHODS: The study was performed on 115 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral acute lung injury. Experimental immunosuppression was reproduced by administration of methotrexate (1.25 mg/kg intraperitoneally, once every 3 days during 3 weeks before infection). During the experiment, mortality, blood oxygen saturation, the concentration of pro-inflammatory cytokines in the lungs, and the severity of lung injury were measured. RESULTS: The presence of experimental immunosuppression led to an exacerbation of acute lung injury in infected animals in terms of mortality and lung damage. Changes in the dynamics of proinflammatory cytokines (TNF-, IL-6, IL-1) in the lungs were observed during acute lung injury. Retarded recovery of the lungs functional activity was noted. CONCLUSIONS: The experimental immunosuppression contributed to the exacerbation of acute lung injury and to an increase in the duration of the pathology. These changes could be associated with an altered process of elimination of the pathogen. The reproduced model of combined pathology was used for searching a therapy for these complications.

scholarly journals Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury

2019 ◽  
Vol 20 (7) ◽  
pp. 1678 ◽  
Author(s):  
Yi-Chen Lee ◽  
Chun-Yu Lin ◽  
Yen-Hsu Chen ◽  
Wen-Chin Chiu ◽  
Yen-Yun Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Lines ◽  
Inflammatory Cytokines ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Epithelial Cell Lines ◽  
Nfκb Pathway ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

scholarly journals Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

2015 ◽  
Vol 90 (4) ◽  
pp. 1812-1823 ◽  
Author(s):  
Michael G. Sugiyama ◽  
Asela Gamage ◽  
Roman Zyla ◽  
Susan M. Armstrong ◽  
Suzanne Advani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Influenza Virus ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Platelet Adhesion ◽  
Human Lung ◽  
Influenza Infection ◽  
Antiplatelet Agent ◽  
Severe Infections ◽  
Lung Endothelium

ABSTRACTLung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCEThere is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have recently shown that the virus can infect human lung endothelial cells, but the functional consequences of this infection are unknown (S. M. Armstrong, C. Wang, J. Tigdi, X. Si, C. Dumpit, S. Charles, A. Gamage, T. J. Moraes, and W. L. Lee, PLoS One 7:e47323, 2012,http://dx.doi.org/10.1371/journal.pone.0047323). Here, we show that this infection causes platelets to adhere to the lung endothelium. Importantly, blocking platelets using two distinct antiplatelet drugs improved survival in a mouse model of severe influenza infection. Thus, platelet inhibition may constitute a novel therapeutic strategy to improve the host response to severe infections with influenza.

scholarly journals Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

2020 ◽  
Author(s):  
Ling Mao ◽  
Ya Zhou ◽  
Longqing Chen ◽  
Lin Hu ◽  
Shiming Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
Lps Challenge ◽  
Mitogen Activated Protein ◽  
Pre Treatment ◽  
Pro Inflammatory Cytokines

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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 Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Huihui Li ◽  
Dapeng Qiu ◽  
Huijuan Yang ◽  
Yuan Yuan ◽  
Lingqin Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Effect ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
Therapeutic Efficacy ◽  
Trichinella Spiralis ◽  
Inflammatory Diseases ◽  
Secretory Products ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a common complication of systemic inflammation or sepsis with high morbidity and mortality. Although many studies have confirmed that helminth-derived proteins had strong immunomodulatory functions and could be used to treat inflammatory diseases, there is no report on the therapeutic effect of excretory-secretory products of Trichinella spiralis adult worms (Ts-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of Ts-AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with Ts-AES, the survival rate of mice with CLP-induced sepsis was significantly increased to 50% for 72 hours after CLP surgery compared to PBS control group with all mice died. The sepsis-induced ALI was largely mitigated characterized by reduced inflammation cell infiltration and pathological changes in lung tissue, with decreased lung injury scores and lung wet/dry weight ratio. The therapeutic efficacy of Ts-AES is associated with stimulated Tregs response with increased regulatory cytokines IL-10 and TGF-β and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of HMGB1, TLR2 and MyD88 in lung tissue was inhibited after treatment of Ts-AES. Our results demonstrated that Ts-AES play an important role in immunomodulation and confer a therapeutic effect on sepsis-induced ALI through inhibiting pro-inflammatory cytokines. The activation of Tregs and increased level of regulatory cytokines IL-10 and TGF-β are possibly involved in the immunomodulatory functions of Ts-AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest Ts-AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.

The effect of aminoguanidine on acute lung injury induced by influenza A/H1N1/PDM09

2020 ◽  
Vol 20 (2) ◽  
pp. 33-44
Author(s):  
Andrei G. Aleksandrov ◽  
Tatiana N. Savateeva-Lyubimova ◽  
Kira I. Stosman ◽  
Arman A. Muzhikyan ◽  
Konstantin V. Sivak
Keyword(s):  
Influenza Virus ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Influenza A ◽  
Structural Changes ◽  
Saturation Index ◽  
Influenza Infection ◽  
Proinflammatory Response ◽  
Influenza Virus A ◽  
Influenza A H1n1

Background. Acute lung injury is one of severe course of influenza infection with mortality up to 40% of patients, despite on etiological and pathogenetic therapy. The aim of the article to study of the effects of aminoguanidine on correcting on acute lung injury induced by influenza virus A/California/7/09MA (mouse-adapted) (H1N1)pdm09, collection Smorodintsev Research Institute of Influenza. Materials and methods. The study was performed on 95 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral infection at a dose of 1 LD50. The mortality was analysed. Levels of advanced glycation end-products (AGEs), proinflammatory cytokines in lung; saturation index and leukocytes marker parameters in blood; pathological and histological studies of lung were performed on 4 and 7 days post infection. Results. Aminoguanidine led to 2-fold decrease in mortality in mice with virus-induced acute lung injury; significantly suppressed the growth of AGEs and proinflammatory cytokine levels in lung; reduced decrease of saturation index and hematological inflammatory markers; decreased level of inflammatory injury in lung tissue. Conclusion. Aminoguanidine relieved virus-induced acute lung injury in mice. These AGEs inhibitor reduced the proinflammatory response and structural changes in respiratory tract epithelial cells induced by reactive carbonyl compounds on cell membrane.

Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice

2015 ◽  
Vol 102 ◽  
pp. 1-11 ◽  
Author(s):  
Faisal Imam ◽  
Naif O. Al-Harbi ◽  
Mohammed M. Al-Harbi ◽  
Mushtaq Ahmad Ansari ◽  
Khairy M.A. Zoheir ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
T Cell ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
T Cell Receptors ◽  
Cell Receptors ◽  
Pro Inflammatory Cytokines

scholarly journals Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

2020 ◽  
Author(s):  
Ling Mao ◽  
Ya Zhou ◽  
Longqing Chen ◽  
Lin Hu ◽  
Shiming Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
Lps Challenge ◽  
Mitogen Activated Protein ◽  
Pre Treatment ◽  
Pro Inflammatory Cytokines

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4 -/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

Sign in / Sign up

Export Citation Format

Share Document