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)

Fifty-seven patients with decompensated cirrhosis were studied prospectively to assess the sensitivity and specificity of early clinical or biological signs of bacterial infection. Among them, 19 had proven infection on admission (7 spontaneous bacterial peritonitis, 5 bacteraemia, 3 urinary tract infections, 2 pneumonia, 1 dental abscess and 1 cholangitis). Fever, polymorphonuclear cell count, fibrinogen and C-reactive protein levels were found to be of little or no help in diagnosing bacterial infection on admission. Interleukin-6 plasma levels were, however, significantly different between infected (median: 1386 pg/ml, range: 237-20,000) and non-infected patients (median: 34 pg/ml, range: 0-4500, p < 0.00001). Levels above 200 pg/ml were always found in infected patients, giving a sensitivity of 100% and a specificity of 74%. C-reactive protein correlated weakly with interleukin-6 levels, indicating a defective acute-phase response in cirrhosis. Tumor necrosis factor alpha plasma levels were less sensitive (95%) and specific (68%) for the diagnosis of bacterial infection at a threshold of 50 pg/ml, but were more closely related to a poor patient outcome. In decompensated cirrhosis, interleukin-6 plasma levels on admission provided the most sensitive and specific tool for the diagnosis of bacterial infection.
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PMID:Interleukin-6: an early marker of bacterial infection in decompensated cirrhosis. 793 Apr 84

A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4+ T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8+ T-cell function (beta2-microglobulin deficient, MHC class I deficient [Beta2m-/-]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh-/-]), and gamma interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg-/-]) or interleukin-4 (C57BL/6J(tm1Cgn29) [IL4-/-]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development. Resistance to reinfection with MoPn was heavily dependent on CD4+ T cells. CD4 T-cell-deficient MHC class II-/- mice were very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance. These mice lacked antibody production but did produce IFN-gamma, apparently by mechanisms involving NK and CD8+ T cells. Neutralization of IFN-gamma in these mice led to a borderline increase in susceptibility, showing a possible role (albeit small) of this cytokine in this setting. Tumor necrosis factor alpha (TNF-alpha) was also present at increased levels in these mice. Igh-/- B-cell-deficient mice which produce no antibody to MoPn were only modestly more susceptible to reinfection than immunized B-cell-intact controls, showing that antibody, including lung immunoglobulin A, is not an absolute requirement for relatively successful host defense in this setting. Levels of lung IFN-gamma and TNF-alpha were elevated in Igh-/- mice compared to those in controls. IL-4-/- mice (deficient in Th2 function) could develop normal resistance to reinfection with MoPn. Conversely, normal mice rendered partially IFN-gamma deficient by antibody depletion were somewhat impaired in their ability to develop acquired immunity to MoPn, again indicating a role for this cytokine in host defense against rechallenge. Of most importance, however, congenitally IFN-gamma-deficient Ifg-/- mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating factor) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma is not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s). In vivo depletion of TNF-alpha significantly increased MoPn levels in the lungs in these mice. Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4+ T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody. Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study.
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PMID:Humoral and cellular immunity in secondary infection due to murine Chlamydia trachomatis. 919 62

Tumor necrosis factor alpha (TNF) has been shown to be an essential cytokine mediator of innate immunity in Klebsiella pneumonia. Recently, a TNF agonist peptide consisting of the 11-amino-acid TNF binding site (TNF70-80) has been shown to possess many of the leukocyte-activating properties of TNF without the associated toxicity when administered locally or systemically. Given the beneficial effects of TNF in gram-negative pneumonia, we hypothesize that the intratracheal (i.t.) administration of TNF70-80 would augment lung innate immunity in mice challenged with intrapulmonary Klebsiella pneumoniae. The administration of TNF70-80 i.t. to CBA/J mice 7 days prior to, but not concomitantly with, the i.t. delivery of 3 x 10(3) CFU of K. pneumoniae resulted in a marked increase in survival compared to that of animals receiving a control peptide i.t. In addition, pretreatment with TNF70-80 resulted in improved bacterial clearance, which occurred in association with enhanced lung myeloperoxidase activity (as a measure of lung polymorphonuclear leukocyte influx), and increased expression of the important activating cytokines TNF, macrophage inflammatory protein-2, interleukin-12, and gamma interferon compared that for animals receiving control peptide. Finally, the administration of TNF70-80 intraperitoneally resulted in enhanced rather than decreased lethality of Klebsiella pneumonia compared to that for animals receiving either TNF70-80 or control peptide i.t. Our studies suggest that the intrapulmonary, but not systemic, administration of the TNF agonist peptide may serve as an important immunoadjuvant in the treatment of murine Klebsiella pneumonia.
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PMID:Intrapulmonary delivery of tumor necrosis factor agonist peptide augments host defense in murine gram-negative bacterial pneumonia. 959 55

Group B streptococci (GBS) are important pathogens in neonatal sepsis and pneumonia. GBS stimulate alveolar macrophages to produce inflammatory cytokines and free oxygen radicals, which can damage the lungs. In several studies, use of exogenous surfactant in term babies has improved outcome related to sepsis and respiratory failure. The role(s) of exogenous surfactant in modulating the inflammatory response produced by this microbe was examined. Tumor necrosis factor alpha (TNF-alpha) production and luminol-enhanced chemiluminescence (LCL), a measure of respiratory burst, were investigated. For measuring TNF-alpha release, RAW 264.7 murine macrophages were pre-incubated with bovine surfactant and stimulated with either lipopolysaccharide, live or heat-killed GBS type Ia. LCL was measured after macrophages were pre-incubated with or without surfactant overnight, then stimulated with GBS or phorbol myristate acetate. Lipopolysaccharide and GBS stimulated TNF-alpha secretion from macrophages that was suppressed by exogenous surfactant in a dose-dependent fashion. GBS and phorbol myristate acetate also increased LCL from macrophages, which was significantly suppressed by pre-incubation of macrophages with exogenous surfactant. We conclude that GBS type Ia stimulates TNF-alpha release and LCL from RAW 264.7 cells and that these responses are suppressed by surfactant. Suppression of inflammatory mediators by exogenous surfactant might improve respiratory disease associated with GBS.
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PMID:Immunomodulation by exogenous surfactant: effect on TNF-alpha secretion and luminol-enhanced chemiluminescence activity by murine macrophages stimulated with group B streptococci. 1133 43

Tumor necrosis factor alpha (TNF-alpha) blocking drugs improve therapy for rheumatic diseases, but the risk of additional immunosuppression and infection is unclear. We report on a patient with rheumatoid arthritis treated with etanercept for 2 years, in addition to methotrexate and prednyliden, who developed fulminant pneumococcal pneumonia with rapid progression to fatal acute respiratory distress syndrome (ARDS) and septic shock. In patients receiving anti-TNF-alpha therapy, especially in combination with corticosteroids, signs of pulmonary infection should be regarded as very serious, as fulminant pneumonia with ARDS and severe sepsis may develop within 24 h.
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PMID:Lethal acute respiratory distress syndrome during anti-TNF-alpha therapy for rheumatoid arthritis. 1620 Mar 83

The incidence of bacterial pneumonia is increased in alcoholic patients. Alcohol consumption has been shown to impair cytokine production. Tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) are critical for host defense against Klebsiella pneumoniae (K. pneumoniae). In order to examine the influence of alcohol on the immune response to infection, we investigated the frequency of TNF-alpha and IFN-gamma produced by splenic T-lymphocytes in a murine model of gram-negative pneumonia initiated after 8 days of alcohol treatment. Thirty-two Balb/c mice were pretreated with ethanol (3 mg/g body weight) or saline intraperitoneally over 8 days. On day 7 half of each group was administered K. pneumoniae. Mice were sacrificed 24 hours later to excise lungs and liver for histological assessment and spleens for cell isolation. IFN-gamma- and TNF-alpha-producing CD4(+) and CD8(+) lymphocytes were determined by FACS analysis. In mice with Klebsiella infection, the percentages of IFN-gamma-producing CD4(+) (P < 0.01) and CD8(+) (P < 0.01) were significantly decreased, the percentages of TNF-alpha-producing CD4(+) (P = 0.01) and CD8(+) (P < 0.01) T cells were significantly elevated after alcohol treatment compared with mice with saline treatment. The histological assessment showed an aggravation of K. pneumoniae-induced pneumonia in alcohol-treated mice. Alcohol differentially affects IFN-gamma and TNF-alpha production in Klebsiella-infected mice. Both effects obviously led to a weakened immune response as seen by increased histological damage. This suggests a role of T cells in the increased susceptibility of the alcoholic host to nosocomial infection due to inadequate cytokine response.
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PMID:Differential effects of ethanol on IFN-gamma- and TNF-alpha-producing splenic T lymphocytes in a murine model of gram-negative pneumonia. 1740 98

Tumor necrosis factor alpha antagonists have proven efficacious for a variety of autoimmune-mediated diseases. However, recent data have highlighted the risk of invasive fungal infections with their use. These agents are typically discontinued when infectious complications occur during therapy; however, the immune reconstitution inflammatory syndrome (IRIS) may be seen after drug cessation. We describe the 1st case of IRIS secondary to cryptococcal pneumonia after cessation of adalimumab.
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PMID:Immune reconstitution inflammatory syndrome after cessation of the tumor necrosis factor alpha blocker adalimumab in cryptococcal pneumonia. 1950 93