Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated a broad spectrum of immunoactive mediators in a mouse model of influenza. ICR mice (4-5 wk old) that were infected with a 10 LD50 dose of influenza A/PR8/34 virus died after 6 days without evidence of bacterial superinfection. Maximal virus titers were reached by day 2 postinfection, whereas the multifocal pneumonia with mononuclear cell infiltration reached its maximum at the end of infection. We measured the cytokines IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IFN-gamma, TNF-alpha, granulocyte (G)/macrophage (M)-CSF, G-CSF, M-CSF, and the lipid mediators leukotriene B4 and platelet-activating factor in the cellfree bronchoalveolar lavage fluid of mice during infection. We found an early increase of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, GM-CSF, IFN-gamma, and leukotriene B4. Levels of these factors peaked between 36 h and day 3 postinfection, with the exception of IL-6 that remained at elevated levels throughout infection. G-CSF and M-CSF increased slowly and reached a maximum by day 5 postinfection. We were unable to detect IL-2, IL-3, or IL-4. PAF remained at the same level throughout infection. Our results suggest that lung-resident cells, and possibly the alveolar macrophages, participate actively in the onset of the inflammatory response against the invading virus. The inability to detect the T cell products IL-2, IL-3, and IL-4 was unexpected considering the role of T cells in the elimination of the virus in infected mice. Our observation confirms thus earlier findings about the inability of specific T cell clones to elicit an unspecific antiviral effect.
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PMID:A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. 132 55

After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in the rat, interleukin-1 alpha/beta (IL-1 alpha/beta) mRNA expression peaks at 1 hour in whole organ RNA preparations of the lung, liver, spleen, and bowel. Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT) injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6 hours, concurrent with the maximum influx of neutrophils (PMNs) into the bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS. A much greater expression of IL-1 and IL-1ra mRNA was observed in PMN-rich BAL cells obtained after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1 and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN-enriched subpopulations from the BAL cells obtained at 6 hours after IT injection of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA preparations after IV and IT injections of LPS is due to the contribution of PMNs that appear in the lung in large numbers after IT injection. Finally, human peripheral blood PMNs were found to express IL-1ra mRNA and protein after in vitro incubation with LPS. PMNs may contribute to the up- and downregulation of their own accumulation by expressing both IL-1 and IL-1ra.
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PMID:Endotoxin-induced cytokine gene expression in vivo. IV. Expression of interleukin-1 alpha/beta and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation. 138 28

The aims of this study were to assess the role played by alveolar macrophages, tumor necrosis factor alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) in pulmonary immunity against Pseudomonas aeruginosa in animals that have been immunized via the gut-associated lymphoid tissue. Following intra-Peyer's patch immunization and subsequent intratracheal challenge with live bacteria, significantly enhanced bacterial clearance from the lungs correlated with an increase in bronchoalveolar neutrophils, increased recruitment and phagocytic activity of alveolar macrophages, and accelerated production of TNF-alpha in the bronchoalveolar space, while levels of IL-1 alpha remained low. Administration of recombinant TNF-alpha in physiological concentrations did not affect the proliferation of P. aeruginosa in vitro, but when given intratracheally to rats at the time of infection, recombinant TNF-alpha significantly increased bacterial clearance from the lungs. In these animals, phagocytic activity of bronchoalveolar neutrophils was enhanced, while the recruitment of alveolar macrophages and neutrophils remained unchanged. In acutely infected nonimmune animals, bronchoalveolar concentrations of soluble IL-1 alpha and TNF-alpha increased until the time of death. Levels of prostaglandin E2 and thromboxane B2 were similar in each experimental group. These results indicate that infection in immune animals enhanced both recruitment and phagocytic activity of alveolar macrophages as well as induced an accelerated production of TNF-alpha. In immune challenged animals, this cytokine enhanced the phagocytic activity of neutrophils and improved bacterial clearance from the lung. Levels of soluble IL-1 alpha and TNF-alpha in nonimmune rats increased consistently following infection until the time of death, thus implicating these cytokines in the pathogenesis of acute P. aeruginosa pneumonia.
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PMID:Pulmonary immunity to Pseudomonas aeruginosa in intestinally immunized rats roles of alveolar macrophages, tumor necrosis factor alpha, and interleukin-1 alpha. 796 Jan 12

Therapeutic thoracic irradiation may induce two late pulmonary injury syndromes: radiation pneumonitis and subsequent pulmonary fibrosis. The alveolar macrophage has been considered a radioresistant cell and not a target cell involved in the pathogenesis of either type of radiation-induced lung injury. Alveolar macrophage-derived cytokines, including interleukin-1 (IL-1) and tumor necrosis factor (TNF), have been demonstrated to participate in inflammatory and fibrotic responses in the lung after various other types of lung injury. To evaluate whether the release of cytokines by alveolar macrophages is induced by radiation doses used clinically, alveolar macrophages recovered from nonsmoking volunteers were exposed in vitro to a single dose of 2 Gy and then maintained in culture for 18 h. Culture supernatants and cell lysates were then recovered and analyzed for IL-1 alpha and IL-1 beta by radioimmunoassay. Supernatants of irradiated alveolar macrophages contained significantly increased amounts of IL-1 alpha (P < 0.04) and IL-1 beta (P < 0.02) as well as total IL-1 (IL-1 alpha and IL-1 beta) (P < 0.02) compared to nonirradiated alveolar macrophages. Cell lysates of irradiated alveolar macrophages also contained increased amounts of IL-1 alpha and IL-1 beta, although differences from controls were not significant. The finding of increased release of IL-1 by alveolar macrophages after exposure to a single, clinically relevant dose of radiation suggests that the function of human alveolar macrophages is likely altered during therapeutic use of thoracic irradiation. Whether this release of IL-1 by alveolar macrophages contributes to early lung inflammation induced by thoracic irradiation is unclear.
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PMID:Release of interleukin-1 by human alveolar macrophages after in vitro irradiation. 821 Mar 36

Fibrosis, characterized by the accumulation of collagen, is a consequence of a chronic inflammatory response. The purpose of this study was to determine if tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta mRNA expression are altered acutely after irradiation, during the so-called "latent" phase of pulmonary injury, and to examine if these alterations persist through the development of pneumonitis and fibrosis. Further, we wished to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by slot blotting and hybridized with radiolabeled cDNA probes encoding for TNF-alpha, IL-1 alpha and IL-1 beta. Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase. It was found that TNF-alpha mRNA levels were increased in C57BL/6 mice at days 1 and 7 postirradiation after 5 Gy and day 14 postirradiation after both 5 and 12.5 Gy, and IL-1 alpha mRNA levels were increased in C57BL/6 mice at days 56, 112 and 182 postirradiation after both 5 and 12.5 Gy, and IL-1 beta mRNA levels in the C3H/HeJ mice were increased at days 56 and 182 postirradiation after 12.5 Gy. In summary, these studies demonstrated early and persistent alterations in TNF-alpha, IL-1 alpha and IL-1 beta mRNA levels even at the lower dose (5 Gy). The temporal relationship between the elevation of these cytokines and the strain-dependent variation in fibrosis response suggests that IL-1 alpha and TNF-alpha contribute to the radiation-induced component of pulmonary fibrosis, whereas IL-1 beta may have a protective function.
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PMID:Early and persistent alterations in the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor alpha mRNA levels in fibrosis-resistant and sensitive mice after thoracic irradiation. 864 37

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.
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PMID:Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis. 917 16

Drug can cause various types of lung damages, with drug-induced pneumonitis (including acute interstitial pneumonia, usual interstitial pneumonia, desquamative interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis obliterans with organizing pneumonia, eosinophilic pneumonia and hypersensitivity pneumonitis) being the most important among them. The incidence and the causative agents of drug induced pneumonitis have varied over time. Before 1980, anticancer agents and gold salts were the main drugs, and the number of causative drugs (61) and case reports was small. Recently, pneumonitis has increasingly been caused by Chinese herbal medicines, antibiotics, chemotherapy agents, anti-inflammatory drugs, analgesics, cytokines, and gold salts, and the number of case reports and drugs involved (177) has increased. Drug-induced pneumonitis has characteristics that depend on the causative agent. Review of our patients and reports in Japan revealed the following. Pneumonitis caused by anti-inflammatory drugs, analgesics, and antibiotics generally develops at 1-2 weeks after starting administration, and bronchoalveolar lavage and histologic examination of lung biopsies reveals the features of eosinophilic pneumonia. Such pneumonitis is associated with a high frequency of a positive drug lymphocyte stimulation test (DLST), and has a good outcome. Conversely, with pneumonitis caused by anticancer and immunosuppressive agents, the onset is often delayed and the disease has features of diffuse interstitial pneumonia and pulmonary fibrosis. The frequency of a positive DLST is low, and the outcome is generally poor. Pneumonitis induced by Chinese herbal medicines, gold salts, and antituberculosis agents has intermediate features between the above two types :i.e., it develops after 2-3 months or six months (gold salts), and resembles either eosinophilic pneumonia, BOOP or interstitial pneumonia. For in vitro identification of causative drugs, the DLST and the leukocyte migration inhibition test (LMIT) are generally used. The latter test is superior in sensitivity, suggesting that the mechanism of this test involves cytokines such as IL-1 alpha, IL-1 beta, IL-2, TNF-alpha, and IL-8.
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PMID:[Drug-induced pneumonitis]. 1006 54

To examine the effects of acid exposure on the adherence of Streptococcus pneumoniae to cultured human tracheal epithelial cells, cells were exposed to acid at various pH levels, and various concentrations of S. pneumoniae were added to the culture medium. The number of S. pneumoniae adhering to cultured human tracheal epithelial cells increased after acid exposure. Y-24180, a specific inhibitor of the receptor for the platelet-activating factor (PAF) and PAF itself decreased the number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the activation of transcription factor nuclear factor (NF)-kappa B and the expression of protein and messenger RNA (mRNA) of the PAF receptor. The pyrrolidine derivative of dithiocarbamate (PDTC), an inhibitor of NF-kappa B, also decreased the number of S. pneumoniae adhering to the cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the content of interleukin (IL)-1 alpha and IL-1 beta in the culture supernatants, but monoclonal antibodies to IL-1 alpha and IL-1 beta failed to inhibit the increased number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. These findings suggest that acid exposure stimulates the adherence of S. pneumoniae to the airway epithelial cells via increases in PAF receptors. Increases in PAF receptor expression may be, in part, mediated via activation of transcription factors and subsequent PAF receptor mRNA expression by acid exposure. Increased adherence of S. pneumoniae may be one of the reasons why pneumonia develops after gastric juice aspiration.
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PMID:Acid exposure stimulates the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells: effects on platelet-activating factor receptor expression. 1130 40