Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin-induced microvascular lung injury in mice is a commonly used experimental model of the acute respiratory distress syndrome (ARDS). The present paper aimed to characterize this popular model in a comprehensive and systematic fashion. Male C57bl/6 mice (n = 5) were administered an LD55 dose of E. coli endotoxin (15 mg/kg, i.p.), and lungs were harvested at several time points and evaluated for injury as well as for expression of a variety of inflammatory mediators. Endotoxin induced many features characteristic of acute microvascular lung injury. These included early (1-2 h) expression of inflammatory mediators (IL-1alpha, IL-1beta, IL-4, IL-6, IL-10, TNF-alpha, interferon-alpha, interferon gamma, and MCP-1) and leukocyte accumulation in lung tissue (lung myeloperoxidase activity 18.5 +/- 7.8 U/g tissue, P < 0.05), followed by pulmonary edema (lung water content index 17.4% +/- 2.5%, P < 0.05) and mortality. Histopathological evaluation of lung tissue was compatible with these findings. The characterization of this murine model of endotoxin-induced microvascular injury will facilitate its utilization in ARDS research.
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PMID:Characterization of a murine model of endotoxin-induced acute lung injury. 1195 30

Exposure of the respiratory tract to lipopolysaccharide (LPS) induces acute local inflammation and tissue injury associated with the various deliveries of LPS. To determine potential association of local inflammatory responses with respiratory tract dysfunction, infiltration of inflammatory cells, production of inflammatory mediators, lung hyperinflation and edema were measured in Wister rats 2, 4, and 24 h after an intratracheal administration of LPS at different doses (5, 50, 500 and 5000 microg/ml/kg). Lung hyperinflation determined by an increased excised lung gas volume was significantly increased 2 and 4 h after LPS instillation and lung edema occurred from 2 h onward. Peak BAL levels of TNFalpha appeared at 2 h, MCP-1 at 4 h, and IL-6 at 2 and 4 h, while BAL levels of IL-1beta were increased during 24 h after the intratracheal instillation of LPS. Neutrophilia in BAL fluid was noted from 2 h post-challenge. Our results demonstrate a clear dose-related change in the lung weight at 4 and 24 h, in the BAL levels of MCP-1 at 4 h, and IL-6 and IL-1beta at 2 and 4 h. It seems important to understand polymorphisms of LPS-induced lung hyperinflation and inflammation. Lung hyperinflation and inflammation may be independent during the development of acute lung injury.
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PMID:Lung inflammatory responses and hyperinflation induced by an intratracheal exposure to lipopolysaccharide in rats. 1552 55

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.
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PMID:San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs. 1587 12

The purpose of this study was to investigate the regulation of lung macrophages (Muvarphis) by Kupffer cells (KCs) in lung injury caused by endotoxemia. Phenotypic differences in tissue Muvarphis were also investigated. Muvarphis were isolated from gadolinium chloride (GdCl(3))- or saline-treated rats 2 h after saline or lipopolysaccharide (LPS) administration. Furthermore, rats were given GdCl(3) 24 h prior to LPS administration, and survival rate was assessed for 24 h. Moreover, lung edema was assessed 9 h after LPS injection. Expression of inflammatory mediators was measured in the liver and lung. KCs were divided into three subpopulations based on size and phagocytosis. The expression of TNF-alpha and MIP-2 was greater in the small KCs and lung Muvarphis, while the expression of IL-6, IL-10, and MCP-1 was greater in the large and intermediate KCs. GdCl(3) eliminated ED2-positive large KCs and did not have any effect on the lung Muvarphis. The number of ED1-positive KCs increased significantly in both organs after LPS challenge and was reduced by GdCl(3). The population of ED2-positive KCs did not change following LPS administration. GdCl(3) completely prevented increases in lung microvascular permeability and mortality after LPS infusion. After LPS administration, expression of TNF-alpha and IL-6 increased rapidly and then decreased gradually in both organs. GdCl(3) inhibited these increases in the liver significantly and enhanced the expression of MCP-1 and IL-10 in the lung 9 h after LPS administration. Thus, the heterogeneous response of KCs to endotoxin leads to production of certain cytokines and chemokines that affect lung function.
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PMID:Role of Kupffer cells in lung injury in rats administered endotoxin 1. 1611 35

To investigate the effects of Gingyo-san (GGS), the traditional Chinese medicinal formula, on the acute lung inflammation induced by LPS in vivo, mice were challenged with intratracheal LPS before treatment with GGS or vehicle. In lung morphology, GGS reduced the infiltration of activated polymorphonuclear neutrophils in the airways, decreased pulmonary edema, reduced nitrosative stress, and improved lung morphology. ELISA or RT-PCR detected the expression of cytokines in BALF and lung tissue. The mechanism of these benefits by treatment with GGS including attenuating expression TNFalpha, IL-1 beta, IL-6, KC, MCP-1, MIP-2, iNOS, and activation of nuclear factor (NF-kappaB and AP-1) in BALF and lung tissue. Particularly, GGS also enhanced the anti-inflammatory cytokine (IL-10) and limited the acute lung inflammation. Therefore, its protection activity against LPS-induced lung inflammatory mediators release might be beneficial in the treatment of endotoxin-associated inflammation.
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PMID:Protective and immunomodulatory effect of Gingyo-san in a murine model of acute lung inflammation. 1727 22

Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1alpha, MIP-2, MCP-1 and IFNgamma) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM-infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects.
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PMID:Pneumonia virus of mice: severe respiratory infection in a natural host. 1847 97

The most dramatic example of defining the pathogenicity of influenza virus A/H5N1 strains is the higher fatality rate of avian influenza epidemic (>50%) occured in Southeast Asia in 1997 comparing to the pandemic caused by influenza virus A/H1N1 in 1918 (5-10%) which was recorded as the most destructive pandemic in the world. When considering the fatal/total case numbers (208/340) reported by World Health Organization in respect of December 14th, 2007, the mortality rate has now reached to 61 percent. Recent studies have shown that the high fatality rate of avian influenza virus infections is a consequence of an overactive inflammatory response and the severity of infection is closely related with virus-induced cytokine dysregulation. The most important feature of A/H5N1 immunopathogenesis is the appearence of hypercytokinemia ("cytokine storm") which is characterized by the extreme (exaggerated) production and secretion of large numbers and excessive levels of pro-inflammatory cytokines. This phenomenon is blamed on the emergence of lethal clinical symptoms such as extensive pulmonary oedema, acute bronchopneumoniae, alveolar haemorrhage, reactive haemophagocytosis, and acute respiratory distress syndrome, associated with necrosis and tissue destruction. Numerous in vitro, in vivo and clinical studies have pointed out that A/H5N1 viruses are very strong inducers of various cytokines and chemokines [Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, IFN-alpha/beta, Interleukin (IL)-6, IL-1, MIP-1 (Macrophage Inflammatory Protein), MIG (Monokine Induced by IFN-gamma), IP-10 (Interferon-gamma-Inducible Protein), MCP-1 (Monocyte Chemoattractant Protein), RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), IL-8], in both humans and animals. The privileged cells of cytokine storm are macrophages and CD8+ T-lymphocytes, while the primary contributor cytokines are TNF-alpha, IL-6 and IFN-gamma. It has been detected that, mutations of some viral genes (NS1, PB2, HA and NA) are responsible for the cytokine storm, by increasing the viral replication rate, expending the tissue tropism, facilitating the systemic invasion and emerging of resistance against the host antiviral response. It has been shown that Glu92 and Ala149 mutations, and carboxyl-terminal ESEV/EPEV motif of NS1 protein have been implicated as determinants of virulence for A/H5N1 strains. In addition, Lys627 mutation in PB2 protein, polybasic aminoacid mutations in the cleavage region of hemagglutinin (HA) polyprotein, and glycosylation and sialylation mutations in HA and neuraminidase (NA) proteins were found to enhance the immune-mediated patology of highly virulent A/H5N1 strains. In this review article, the immunopathogenesis of influenza infection and the mechanisms of cytokine storm caused by influenza A/H5N1 viruses have been discussed under the light of recent literature.
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PMID:[Cytokine storm in avian influenza]. 1869 37

We report the pathological and virological findings of the first autopsy case of the 2009 pandemic influenza (A/H1N1pdm) virus infection in Japan. A man aged 33 years with chronic heart failure due to dilated cardiomyopathy, mild diabetes mellitus, atopic dermatitis, bronchial asthma, and obesity died of respiratory failure and multiple organ dysfunction syndrome. Macroscopic examination showed severe pulmonary edema and microscopically the lung sections showed very early exudative-stage diffuse alveolar damage (DAD). Immunohistochemistry revealed proliferation of the influenza (A/H1N1pdm) virus in alveolar epithelial cells, some of which expressed SAalpha2-3Gal on the cell surface. Influenza (A/H1N1pdm) virus genomic RNA and mRNA were also detected in alveolar epithelial cells. Real-time PCR revealed 723 copies/cell in the left lower lung section from which the influenza (A/H1N1pdm) virus was isolated. Electron microscopic analysis revealed filamentous viral particles in the lung tissue. The concentrations of various cytokines/chemokines in the serum and the autopsied lung tissue were measured. IL-2R, IL-6, IL-8, IL-10, IFN-alpha, MCP-1, and MIG levels were elevated in both. These findings indicated a case of viral pneumonia caused by influenza (A/H1N1pdm) virus infection, showing characteristic pathological findings of the early stage of DAD.
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PMID:The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination. 2009 68

INTRODUCTION: Evaluation of the systemic inflammatory status following major orthopedic trauma has become an important adjunct in basing post-injury clinical decisions. In the present study, we examined the correlation of serum and lung inflammatory marker levels following bilateral femur fracture. MATERIALS AND METHODS: 45 Sprague Dawley rats underwent sham operation or bilateral femoral intramedullary pinning and mid-diaphyseal closed fracture via blunt guillotine. Animals were euthanized at specific time points after injury. Serum and lung tissue were collected, and 24 inflammatory markers were analyzed by immunoassay. Lung histology was evaluated by a blinded pathologist. RESULTS: Bilateral femur fracture significantly increased serum markers of inflammation including interleukin (IL)-2, IL-6, IL-10, GM-CSF, KC/GRO, MCP-1, and WBC. Femur fracture significantly increased serum and lung levels of IL-1a and KC/GRO at 6 hours. Lung levels of IL-6 demonstrated a trend towards significance. Histologic changes in pulmonary tissue after fracture included pulmonary edema and bone elements including cellular hematopoietic cells, bone fragments and marrow emboli. DISCUSSION AND CONCLUSION: Our results indicate that bilateral femur fracture with fixation in rats results in increases in serum markers of inflammation. Among the inflammatory markers measured, rise in the serum KC/GRO (CINC-1), a homolog to human IL-8, correlated with elevated levels of lung KC/GRO. Ultimately, analysis of serum levels of KC/GRO (CINC-1), or human IL-8, may be a useful adjunct to guide clinical decisions regarding surgical timing.
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PMID:Correlation of measurable serum markers of inflammation with lung levels following bilateral femur fracture in a rat model. 2144 11

The swine-origin H1N1 virus which emerged in 2009 resulted in the first influenza pandemic of the 21(st) century. Although the majority of infections were moderate, a significant proportion of infections were severe and characterized by acute respiratory distress syndrome and pulmonary edema. We compared two isolates from the 2009 H1N1 pandemic; A/California/07/09 (CA/07) and A/Netherlands/602/09 (NL/602) viruses that share greater than 99% sequence identity. Though genetically similar, these viruses exhibit contrasting pathological effects. Mice that were infected with 800 plaque forming unit (PFU) of CA/07 virus rapidly lost weight, which was concurrent with detection of high pulmonary concentrations of MCP-1, MIG, IP-10 and TIMP-1. Initially, severe bronchiolar epithelial necrosis and acute respiratory distress was observed, followed by marked bronchiolar epithelial hyperplasia. Mononuclear cell infiltration was initially localized to perivascular and peribronchiolar interstitium and then spread to adjacent alveoli. Infiltrating cells were phenotypically CD11b(hi), F4/80(lo). In contrast, when mice were infected with 800 PFU of NL/602 virus, minimal weight loss was observed, and concentrations of cytokines in the lung were significantly lower. Inflammation was primarily restricted to the bronchioles and perivascular interstitium with minimal spread to alveoli. Infiltrating cells include foamy macrophages and surface markers were characterized as CD11b(lo/-), F4/80(hi). These two genetically similar viruses can be useful strains with which to investigate immune-regulatory determinants of pathogenesis of influenza virus.
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PMID:Closely related influenza viruses induce contrasting respiratory tract immunopathology. 2408 62


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