UMLS:C0034063 - FACTA Search

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Query: UMLS:C0034063 (pulmonary edema)
10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the production of proinflammatory cytokines by the lung during high mechanical stretch in vivo. To do this, we subjected rats to high-volume (42 ml/kg tidal volume [VT]) ventilation for 2 h. The animals developed severe pulmonary edema and alveolar flooding, with a high protein concentration in bronchoalveolar lavage fluid (BALF). The animals' BALF contained no tumor necrosis factor (TNF)-alpha, negligible amounts of interleukin (IL)-1beta, and less than 300 pg/ml of the chemokine macrophage inflammatory protein (MIP)-2, an amount similar to that found in rats ventilated with 7 ml/kg VT. Systemic cytokine levels were below the detection threshold. Because isolated lungs have been shown to produce high levels of proinflammatory cytokines when ventilated with a similarly high VT for the same duration (Tremblay, et al. J Clin Invest 1997;99:944-952), we reconsidered this specific issue. We ventilated isolated, unperfused rat lungs for 2 h with 7 ml/kg or 42 ml/kg VT, or maintained them in a statically inflated state. Negligible amounts of TNF-alpha were found in the BALF whatever the ventilatory condition applied. The BALF IL-1beta concentration was slightly elevated and higher in lungs ventilated with 42 ml/kg VT than in those ventilated with 7 ml/kg VT or in statically inflated lungs (p < 0.05). The BALF MIP-2 concentration was moderately elevated in all isolated lungs (200 to 300 pg/ml), and was slightly higher (p < 0.05) in lungs ventilated with 42 ml/kg VT. After lipopolysaccharide (LPS) challenge, high levels of TNF-alpha, IL-1beta, and MIP-2 were found in the animals' plasma before the lungs were removed. Negligible amounts of TNF-alpha and IL-1beta were retrieved from the BALF of statically inflated lungs. The concentrations of TNF-alpha and IL-1beta were higher in the BALF of ventilated lungs (p < 0.001). The TNF-alpha level did not differ with the magnitude of VT, whereas the level of IL-1beta was significantly higher in BALF of lungs ventilated with 42 ml/kg VT (p < 0.01). The MIP-2 concentrations were similar for the two ventilatory conditions. These results suggest that ventilation that severely injures lungs does not lead to the release of significant amounts of TNF-alpha or IL-1beta by the lung in the absence of LPS challenge but may increase lung MIP-2 production.
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PMID:Production of inflammatory cytokines in ventilator-induced lung injury: a reappraisal. 1131 28

Urban air consists of a combination of environmental pollutants. Recent studies have suggested that normally innocuous doses of a particular pollutant may be rendered more toxic to the lung if primed by earlier events. Pulmonary inflammation has been observed in humans and in many animal species after endotoxin and ozone exposures. The present study was designed to test the hypothesis that inhalation of low levels of endotoxin following ozone exposure will potentiate ozone-induced lung injury. We exposed 8-week-old C57BL/6J mice to 1 ppm ozone for 24 hours; inhalation of low-dose endotoxin (37.5 EU) for 10 minutes; or 1 ppm ozone immediately followed by endotoxin inhalation (37.5 EU). The mice were examined 4 or 24 hours post exposure. After 24 hours of recovery, significant increases were measured in bronchoalveolar lavage (BAL) fluid levels of protein and lavageable polymorphonuclear neutrophils (PMNs) after coexposure to ozone followed immediately by endotoxin inhalation as compared to exposures individually. Messages encoding macrophage inflammatory protein (MIP)-1beta, MIP-1alpha, MIP-2, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1alpha, IL-1beta, IL-1Ra, IL-6, and Macrophage Migration Inhibitory Factor (MIF) were significantly elevated 24 hours post ozone followed by endotoxin as compared to exposure to ozone or endotoxin individually. These results demonstrate that preexposure to ozone, which primarily attacks the epithelium, can cause sensitization to a secondary stimulus through a mechanism that culminates in a greater and prolonged onset of inflammatory cell recruitment, pulmonary edema, and increased expression of chemokine and cytokine messages.
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PMID:Endotoxin potentiates ozone-induced pulmonary chemokine and inflammatory responses. 1221 10

The acute respiratory distress syndrome (ARDS) is a major cause of morbidity after injury. We hypothesized that alveolar macrophage (AMPhi) chemokine and cytokine release after hemorrhage and sepsis is regulated by NF-kappaB and MAPK. Adult male rats underwent soft tissue trauma and hemorrhagic shock (~90 min) followed by crystalloid resuscitation. Sepsis was induced by cecal ligation and puncture (CLP) 20 h after resuscitation. AMPhi were harvested, and TNF-alpha, IL-6, and macrophage inflammatory protein (MIP)-2 release and serum IL-6 and TNF-alpha levels were measured at 5 h after HCLP. Lung tissues were analyzed for activation of NF-kappaB, myeloperoxidase activity, and wet/dry weight ratio. In control animals, AMPhi were stimulated with LPS with or without inhibitors of NF-kappaB and MAPK. Serum TNF-alpha and IL-6 levels and spontaneous AMPhi TNF-alpha and MIP-2 release were elevated (P < 0.05) after HCLP, concomitantly with the development of lung edema and leukocyte activation. Activation of NF-kappaB increased in lungs from the hemorrhage and CLP group compared with shams. Inhibition of NF-kappaB or the upstream MAPK significantly decreased LPS-stimulated AMPhi activation. Because enhanced release of inflammatory mediators by AMPhi may contribute to ARDS after severe trauma, inhibition of intracellular signaling pathways represents a target to attenuate organ injury under those conditions.
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PMID:Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappaB and MAPK/ERK mechanisms. 1222 57

We have recently identified the alpha-chemokine mob-1 as a highly inducible gene in several rat models of microvascular lung injury, whose expression was suppressed by inhibition of tumor necrosis TNF-alpha (TNF-alpha). This work provides further insight into the relationship between mob-1 and TNF-alpha in the development of lung injury assessed by pulmonary edema and leukosequestration. First, pulmonary mob-1 and TNF-alpha were upregulated in animals subjected to lung injury produced by the intratracheal administration of recombinant TNF-alpha and recombinant mob-1, respectively. Second, mob-1 inhibition by intratracheal anti-mob-1 antibody attenuated lung injury induced by recombinant TNF-alpha. Third, pretreatment with anti-TNF-alpha monoclonal antibody administered intratracheally abrogated recombinant mob-1-induced microvascular lung injury. In vitro, mob-1 and TNF-alpha increased each other's production in RAW 264.7 cells and mob-1 or TNF-alpha inhibition prevented endotoxin-induced upregulation of TNF-alpha or mob-1, respectively, from these cells. Together, these data suggest that mob-1 and TNF-alpha interact to promote lung inflammation.
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PMID:MOB-1 and TNF-alpha interact to induce microvascular lung injury. 1235 28

Acute lung injury (ALI) leading to respiratory distress is a common sequela of shock/trauma, however, modeling this process in mice with a single shock or septic event is inconsistent. One explanation is that hemorrhage is often just a "priming insult," thus, secondary stimuli may be required to "trigger" ALI. To test this we carried out studies in which we assessed the capacity of hemorrhage alone or hemorrhage followed by septic challenge (CLP) to induce ALI. Lung edema, bronchoalveolar lavage interleukin (IL)-6, alveolar congestion, as well as lung IL-6, macrophage inflammatory protein (MIP)-2, and myeloperoxidase (MPO) activity were all increased in mice subjected to CLP at 24 but not 72 hours following hemorrhage. This was associated with a marked increase in the susceptibility of these mice to septic mortality. Peripheral blood neutrophils derived from 24 hours post-hemorrhage, but not Sham animals, exhibited an ex vivo decrease in apoptotic frequency and an increase in respiratory burst capacity, consistent with in vivo "priming." Subsequently, we observed that adoptive transfer of neutrophils from hemorrhaged but not sham-hemorrhage animals to neutropenic recipients reproduce ALI when subsequently septically challenged, implying that this priming was mediated by neutrophils. We also found marked general increases in lung IL-6, MIP-2, and MPO in mice deficient for toll-like receptor (TLR-4) or the combined lack of TLR-4/FasL. However, the TLR-4 defect markedly attenuated neutrophil influx into the lung while not altering the change in local cytokine/chemokine expression. Alternatively, the combined loss of FasL and TLR-4 did not inhibit the increase in MPO and exacerbated lung IL-6/MIP-2 levels even further.
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PMID:Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. 1246 42

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a peptide with broad anti-inflammatory effects. The present research was designed to determine production and effects of alpha-MSH in acute bleomycin-induced lung injury in rats. Intratracheal bleomycin instillation induced alpha-MSH expression in lung infiltrating cells and a marked peptide increase in the circulation. In experiments on the therapeutic potential of alpha-MSH on lung injury, we determined influences of the synthetic alpha-MSH analogue [Nle4-dPhe7]-alpha-MSH (NDP-alpha-MSH) on pulmonary edema, circulating nitric oxide, and gene expression profile in lungs 8 and 24 h after bleomycin instillation. Three main gene categories, known to be involved in the development of acute lung injury, were explored: stress response, inflammation, and fluid homeostasis. Peptide treatment was associated with a significant reduction in interstitial edema, with a virtually normal wet/dry weight ratio. Several stress-related genes, which were either upregulated or reduced by bleomycin, were only marginally altered during NDP-alpha-MSH treatment. NDP-alpha-MSH prevented bleomycin-related transcriptional alterations in genes involved in lung fluid homeostasis, including upregulation of Na/K-transporting ATPase and epithelial sodium channels and downregulation of cystic fibrosis transmembrane conductance regulator. Bleomycin-induced expression of proinflammatory and profibrotic factors (interleukin 6, tumor necrosis factor-alpha, transforming growth factor-beta1, and inducible nitric oxide synthase) and chemokines (chemokine [C-C motif] ligand 2 and chemokine [C-C motif] ligand 5) was likewise significantly reduced by NDP-alpha-MSH. In conclusion, treatment with the alpha-MSH analogue NDP-alpha-MSH greatly improved the clinical and molecular picture of bleomycin-induced lung injury. Treatment with alpha-MSH-related agents can exert beneficial effects in acute lung injury.
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PMID:Production and effects of alpha-melanocyte-stimulating hormone during acute lung injury. 1730 15

Blunt chest trauma resulting in pulmonary contusion with an accompanying acute inflammatory response is a common but poorly understood injury. We report that Toll-like receptor (TLR) 2 participates in the inflammatory response to lung injury. To show this, we use a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans based on histologic, morphologic, and biochemical criteria of acute lung injury. The inflammatory response to pulmonary contusion in our mouse model is characterized by pulmonary edema, neutrophil transepithelial migration, and increased expression of the innate immunity proinflammatory cytokines IL 1beta and IL 6, the adhesion intracellular adhesion molecule 1, and chemokine (CXC motif) ligand 1. Compared with wild-type animals, contused Tlr2(-/-) mice have significantly reduced pulmonary edema and neutrophilia. These findings are associated with decreased levels of circulating chemokine (CXC motif) ligand 1. In contrast, systemic IL 6 levels remain elevated in the TLR2-deficient phenotype. These results show that TLR2 has a primary role in the neutrophil response to acute lung injury. We suggest that an unidentified noninfectious ligand generated by pulmonary contusion acts via TLR2 to generate inflammatory responses.
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PMID:Toll-like receptor 2 participates in the response to lung injury in a murine model of pulmonary contusion. 1755 51

Our previous studies revealed that the presence in lung fluids of anti-IL-8 autoantibody:IL-8 immune complexes is an important prognostic indicator for the development and outcome of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Anti-IL-8:IL-8 complexes purified from lung edema fluids trigger chemotaxis of neutrophils, induce activation of these cells, and regulate their apoptosis, all via IgG receptor, FcgammaRIIa. Importantly, increased levels of FcgammaRIIa are present in lungs of patients with ARDS, where FcgammaRIIa is partially associated with anti-IL-8:IL-8 complexes. In the current study, we demonstrate the ability of anti-IL-8:IL-8 complexes to promote an inflammatory phenotype of human umbilical vein endothelial cells via interaction with FcgammaRIIa. Human umbilical vein endothelial cells cultured in the presence of the complexes become activated, as shown by increased phosphorylation of ERK, JNK, and Akt, and augmented nuclear translocation of NF-kappaB. Anti-IL-8:IL-8 complexes also up-regulate expression of intracellular adhesion molecule (ICAM)-1 on the cell surface. Furthermore, we detected increased levels of ICAM-1 on lung endothelial cells from mice in which lung injury was induced by generating immune complexes in alveolar spaces. On the other hand, ICAM-1 expression was unchanged in lungs of gamma chain-deficient mice, lacking receptors that interact with immune complexes. Moreover, in lung tissues from patients with ARDS, anti-IL-8:IL-8 complexes were associated with endothelial cells that expressed higher levels of ICAM-1. Our current findings implicate that anti-chemokine autoantibody:chemokine immune complexes, such as IL-8:IL-8 complexes, may contribute to pathogenesis of lung inflammation by inducing activation of endothelial cells through engagement of IgG receptors.
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PMID:Anti-chemokine autoantibody:chemokine immune complexes activate endothelial cells via IgG receptors. 1910 44

Endogenous purines, including inosine, have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for these effects has been shown to be between 200 and 600 mg kg(-1) because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic resistant purine analog, INO-2002, exerts anti-inflammatory effects in an animal model of acute respiratory distress syndrome. Mice challenged with intratracheal LPS (50 microg) were treated with INO-2002 (30 or 100 mg kg(-1), i.p.) in divided doses at either 1 and 12 h or at 5 and 16 h. After 24 h, bronchoalveolar lavage fluid was obtained to measure leukocyte infiltration by myeloperoxidase levels, lung edema by protein levels, and proinflammatory chemokine (macrophage inflammatory protein 1alpha) and cytokine (TNF-alpha, IL-1, and IL-6) levels. INO-2002 (30 and 100 mg kg(-1)) reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by bronchoalveolar lavage fluid reduction in levels of myeloperoxidase and protein. INO-2002 also downregulated expression of the proinflammatory mediators macrophage inflammatory protein 1alpha, TNF-alpha, IL-1, and IL-6. Delaying the start of treatment by 5 h after LPS administration affected the potency of INO-2002 protective effects, with 100 but not 30 mg kg(-1) having anti-inflammatory effects. The inosine analog INO-2002 largely suppressed LPS-induced inflammation in vivo at doses lower than those needed for the naturally occurring purine inosine. These data support the proposal that purine analogs, resistant to metabolic breakdown, may represent a useful addition to the therapy of acute respiratory distress syndrome.
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PMID:The novel inosine analogue INO-2002 exerts an anti-inflammatory effect in a murine model of acute lung injury. 1917 45

Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1-phosphate (S1P), a ligand for a family of G protein-coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P(2) receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E-triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P(2) antagonist JTE-013 and in S1P(2)-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P(2) on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.
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PMID:Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema. 2019 30

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