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)

C receptor-1 is a protein involved in the regulation of C3 and C5-convertases. Recombinant human soluble C receptor-1 has recently been produced and shown to reduce infarct size in a rat model of myocardial ischemia/reperfusion injury. The present study aimed to investigate whether recombinant human soluble C receptor-1 exerts any protective effect on pulmonary injury produced in a rodent model of adult respiratory distress syndrome. In this model, Escherichia coli endotoxin (LPS, 0.1 microgram/kg) combined with platelet-activating factor (1 pmol/kg/min over 60 min, n = 10) caused microvascular lung injury characterized by elevation of myeloperoxidase activity, deposition of C3 and C5b-9 on the endothelium of pulmonary vessels, and pulmonary edema. Furthermore, bronchoalveolar lavage revealed increased neutrophil count and elevated protein concentration. These pulmonary responses were associated with elevated serum TNF-alpha. Pretreatment (10 min, i.v.) with recombinant human soluble C receptor-1 at 10 mg/kg (n = 13), but not at 1 mg/kg, prevented the LPS/platelet-activating factor-induced pulmonary edema (p less than 0.01) and changes in the bronchoalveolar lavage fluid cell count (p less than 0.01) and protein concentration (p less than 0.05), and attenuated the deposition of C3 and C5b-9 to lung vessels. There was no effect on lung myeloperoxidase activity and serum TNF-alpha. Also, C depletion by cobra venom factor (500 U/kg, i.v.) eliminated the pulmonary edema and elevated leukocyte count in bronchoalveolar lavage fluid, but had no effect on lung myeloperoxidase activity and serum TNF-alpha. These data suggest that C factors may play an important role in the pathophysiology of adult respiratory distress syndrome.
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PMID:Role of complement in endotoxin/platelet-activating factor-induced lung injury. 132 80

Tumor-reactive antibodies coupled to ricin or its A-chain (immunotoxins) have been used in rodents and humans to treat a variety of neoplastic diseases. Side-effects of such treatment include hepatotoxicity, vascular leak syndrome, myalgia and low grade fever. At high doses, severe toxicities include liver damage, pulmonary edema, aphasia, rhabdomyolysis and kidney failure. There have been a limited number of toxicologic studies on uncoupled ricin or its A-chain and none on deglycosylated A-chain. Since the latter has been utilized in "second generation" immunotoxins, the current studies were carried out to evaluate the toxicities induced by deglycosylated ricin A-chain (dgA) in mice. The administration of dgA to normal BALB/c mice causes early (24 h) weight loss and late (10 day) accumulation of ascites. These effects could be partially altered by changing the route of injection of dgA from i.v. to i.p. Thus, i.p. administration caused weight loss but not ascites, whereas i.v. administration caused both. Weight loss was associated with reduced fluid intake by the treated mice, and was not associated with increased levels of serum TNF-alpha. SCID mice injected with the same dose of dgA as normal BALB/c mice developed ascites, but it was of lesser severity, suggesting that a functional immune system, differences in microbial flora, or strain differences may be involved in the development of ascites.
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PMID:The toxicity of chemically deglycosylated ricin A-chain in mice. 162 27

Acid aspiration-induced systemic organ injury is mediated by the sequestration of activated neutrophils (PMN). In other settings cytokines have been shown to increase neutrophil-endothelial adhesion, a requisite for injury. This study tests whether the systemic leukosequestration and permeability following localized aspiration is mediated by tumor necrosis factor (TNF)-alpha-induced synthesis of an adhesion protein. Anesthetized rats underwent tracheostomy and insertion of a fine-bore cannula into the anterior segment of the left lung. This was followed by the instillation of either 0.1 mL 0.1 N HCI (n = 18) or 0.1 mL saline in control rats (n = 18). Localized aspiration induced generalized pulmonary leukosequestration with 95 PMN/10 high-power fields (HPF) in the aspirated lung and 46 PMN/10 HPF in the nonaspirated lung, higher than control values of 7 PMN/10 HPF and 5 PMN/10 HPF in saline- and nonsaline-aspirated sides, respectively (p less than 0.05). The leukosequestration was associated with permeability edema shown by increased protein concentrations in bronchoalveolar lavage (BAL) of 3900 micrograms/mL in the aspirated and 2680 micrograms/mL in the nonaspirated side, higher than saline with 482 micrograms/mL and 411 micrograms/mL, respectively (p less than 0.05). There was generalized pulmonary edema following aspiration measured by increase in wet-to-dry weight ratios (w/d) of 6.6 in the aspirated and 5.1 in the nonaspirated lung, higher than control values of 3.5 and 3.4, respectively (p less than 0.05). Localized aspiration led to systemic leukosequestration documented by increases in myeloperoxidase activity (units/g tissue) of 2.2 and 1.7 in heart and kidney, higher than control values of 0.3 and 0.4, respectively (p less than 0.05). This event was associated with edema of these organs with w/d ratios of 4.6 and 4.3, relative to control values of 3.0 and 3.4 (p less than 0.05). Treatment of animals (n = 18) 20 minutes after aspiration with anti-TNF-alpha antiserum (rabbit anti-murine) but not normal rabbit serum (n = 18) reduced lung leukosequestration in the aspirated and nonaspirated segments (61 and 32 PMN/10HPF), BAL protein concentration (1490 and 840 micrograms/mL), and w/d ratio (4.3 and 3.7) (all p less than 0.05). In the heart and kidney there were reductions in myeloperoxidase activity (0.7 and 0.6) and w/d ratio (3.5 and 3.6) (both p less than 0.05). Treatment of rabbits (n = 18) with the protein synthesis inhibitor cycloheximide, 0.2 mg/kg/hr was as effective as TNF-alpha antiserum in modifying aspiration injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tumor necrosis factor-alpha mediates acid aspiration-induced systemic organ injury. 222 16

The recombinant cytokines IFN-gamma and TNF-alpha stimulate several macrophage-mediated functions important in host defense. However, systemic administration of cytokines may be limited by significant host toxicity. We investigated whether aerosolized cytokines can stimulate alveolar macrophage and blood monocyte function, and whether they induce an inflammatory response in the lungs of normal rats. We found that aerosolized murine rIFN-gamma or recombinant human TNF-alpha increased IL-1 production by both alveolar macrophages and blood monocytes for at least 5 days after administration. Furthermore, murine rIFN-gamma increased the expression of Ia Ag on alveolar macrophages and human rTNF-alpha increased alveolar macrophage- and blood monocyte-mediated tumor lysis. Sequential aerosolization of IFN-gamma and TNF-alpha significantly increased both IL-1 release and Ia expression compared to either cytokine administered alone. Aerosolized human rTNF-alpha achieved lung levels comparable to those produced by an i.v. TNF-alpha dose reported to cause diffuse organ injury and death in rats. However, plasma TNF-alpha levels were several thousand-fold lower after aerosol administration. Aerosolized cytokines did not induce lung edema or an inflammatory cell infiltrate within the airways or alveoli. Aerosolized human rTNF-alpha alone, or murine rIFN-gamma and human rTNF-alpha, induced margination of leukocytes in pulmonary blood vessels 1 day after aerosolization, and a few small foci of pulmonary hemorrhage 5 days later. We conclude that aerosol administration of IFN-gamma or TNF-alpha enhances both pulmonary and systemic monocyte function, and that the combination of IFN-gamma and TNF-alpha produce additive or synergistic effects. Aerosolized cytokines induce only a minimal pulmonary inflammatory response. Aerosolized TNF-alpha produces high cytokine levels in the lung but very low uptake into the circulation.
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PMID:Lung-specific delivery of cytokines induces sustained pulmonary and systemic immunomodulation in rats. 328 35

Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.
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PMID:Neutrophil inhibitory factor prevents neutrophil-dependent lung injury. 759 91

During strenuous exercise in endurance athletes, monocytes are activated and there is an acute inflammation and hypoxemia possibly due to lesional pulmonary edema. IL-6 and TNF-alpha released by monocytes may be implicated in the acute phase of lesional pulmonary edema. A study was carried out to determine whether TNF-alpha and IL-6 are released during strenuous exercise, and, if adrenalin released during exercise alters their generation. Ten young and six master athletes underwent an incremental exercise test. Arterial blood was drawn at rest, at the end of the exercise, and 20 minutes afterwards. Monocytes were isolated and incubated for 18 hours in the presence or absence of adrenalin. Il-6 and TNF-alpha were measured in monocyte supernatants. The spontaneous release of IL-6 or TNF-alpha was increased in young athletes when compared to older subjects. The spontaneous release of TNF-alpha was increased, but not significantly, by exercise and there was no correlation between the release of IL-6 and TNF-alpha and lung function measured during hypoxemia. Adrenalin inhibited the release of IL-6 or TNF-alpha. Correlations were observed between the in vitro release of IL-6 or TNF-alpha and age, VO2max, maximal ventilation and maximal power output of the subjects.
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PMID:Release of cytokines by blood monocytes during strenuous exercise. 806 68

In a murine ear-swelling model, we demonstrated a unique hypersensitivity response and defined it as early-type hypersensitivity (ETH). ETH was characterized by increased vasopermeability and edematous change that occurred within 1 h at the site of Ag challenge. In this study, intranasal challenge with Dermatophagoides farinae (Df) on Df-sensitized BALB/c mice induced an ETH response in the lungs. The lung ETH was manifested by an increase in wet lung weight, production of TNF-alpha in bronchoalveolar lavage fluids, and hyperemia and edematous change around vessels of small airways 1 h after Ag provocation. The challenged animals subsequently developed airway inflammation, beginning with a neutrophilic infiltrate which was followed by lymphocytes and eosinophils. The Df-induced eosinophilia was Ag-specific and maximal at 48 h after challenge. At this time, the trachea from sensitized mice also exhibited hyperreactivity to carbachol. Pretreatment with anti-CD4+ mAb significantly decreased the recruitment of eosinophils in bronchoalveolar lavage fluids. An enhanced expression of pulmonary endothelial vascular cell adhesion molecule-1 was noted as early as 6 h after challenge. Anti-Df Abs of IgG class, but not IgE class, were detected in Df-immunized mice at the time of challenge. Furthermore, Df challenge induced a stronger eosinophil response in BALB/c mice (H-2d) than in B10.BR (H-2k) mice. B10.BR mice also did not exhibit pulmonary edema or ETH of ear swelling 1 h after challenge. These data suggest that an ETH-associated 1 h pulmonary edematous change was induced by intranasal challenge of Df in Df-sensitized mice, and that the ETH might contribute to the development of subsequent pulmonary inflammation and eosinophilia.
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PMID:Early-type hypersensitivity-associated airway inflammation and eosinophilia induced by Dermatophagoides farinae in sensitized mice. 859 45

To understand the pathophysiology of high-altitude pulmonary edema (HAPE), we examined the pathway of adaptation to high altitude in lifelong of Tibet. The Tibetan natives had higher exercise performance, but lower maximal oxygen uptake and lower blood lactate concentrations than did acclimatized Han newcomers. Clinical and basic studies done to determine the pathophysiologic characteristics of 47 patients with HAPE and of subjects susceptible to HAPE. The altitude of onset was 2,680 m to 3,190 m above sea level. Results of hemodynamic studies and the presence of protein-rich edema fluid indicated that HAPE is noncardiogenic and is a type of increased permeability edema. The levels of IL-1 beta, IL-6, IL-8, and TNF-alpha in bronchoalveolar lavage fluid from subjects with HAPE were high on admission. The subjects susceptible to HAPE had much greater increases in an index of pulmonary vascular resistance than did the controls, which resulted in much higher levels of pulmonary arterial pressure during both acute hypoxia and hypobaria. The subjects susceptible to HAPE also has blunted hypoxic ventilatory drives. We studied whether human leukocyte antigen DR-6 functions as a genetic predisposition to HAPE. The frequency of DR-6 was increased in the subjects susceptible to HAPE, which suggests that they have a constitutional abnormality in the pulmonary circulatory, and ventilatory responses to hypoxia and hypobaria, and that genetic factors may be involved in the development of HAPE.
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PMID:[High-altitude pulmonary edema in Japan]. 875 74

To evaluate the pathogenesis of high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage (BAL) and pulmonary hemodynamic studies in seven patients with HAPE at its early stage. We measured cell counts, biochemical contents, and concentrations of pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha and of anti-inflammatory cytokines including IL-1 receptor antagonist (ra) and IL-10 in the BAL fluid (BALF). All patients showed increased counts for total cells, alveolar macrophages, neutrophils and lymphocytes, and markedly elevated concentrations of proteins, lactate dehydrogenase, IL-1beta, IL-6, IL-8, TNF-alpha and IL-1ra. The levels of IL-1alpha and IL-10 were not increased. Patients also showed pulmonary hypertension with normal wedge pressure. Both the driving pressure obtained as pulmonary arterial pressure minus wedge pressure and the PaO2 under room air were significantly correlated with the concentrations of IL-6 and TNF-alpha in the BALF. These findings suggest that the inflammatory cytokines play a role at the early stage of HAPE and might be related to pulmonary hypertension.
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PMID:Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema. 962 35

The mechanism of cytokine-induced shock remains poorly understood. The combination of IL-2 and IL-12 has synergistic antitumor activity in vivo, yet has been associated with significant toxicity. We examined the effects of IL-2 plus IL-12 in a murine model and found that the daily, simultaneous administration of IL-2 and IL-12 resulted in shock and 100% mortality within 4 to 12 days depending on the strain employed. Mice treated with IL-2 plus IL-12 exhibited NK cell apoptosis, pulmonary edema, degenerative lesions of the gastrointestinal tract, and elevated serum levels of proinflammatory cytokines and acute phase reactants. The actions of TNF-alpha, IFN-gamma, macrophage-inflammatory protein-1alpha, IL-1, IL-1-converting enzyme, Fas, perforin, inducible nitric oxide synthase, and STAT1 did not contribute to the observed toxicity, nor did B or T cells. However, toxicity and death from treatment with IL-2 plus IL-12 could be completely abrogated by elimination of NK cells. These results suggest that the fatal systemic inflammatory response induced by this cytokine treatment is critically dependent upon NK cells, but does not appear to be mediated by the known effector molecules of this cellular compartment. These data may provide insight into the pathogenesis of cytokine-induced shock in humans.
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PMID:A fatal cytokine-induced systemic inflammatory response reveals a critical role for NK cells. 1020 41


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