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

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), we studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, nine with severe pneumonia uncomplicated by ARDS, and seven mechanically ventilated with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, we identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor-alpha (TNF alpha) in plasma, and both spontaneous and lipopolysaccharide-induced TNF alpha production by cultured monocytes. These biologic expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF-alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.
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PMID:Subpopulation of hyperresponsive polymorphonuclear neutrophils in patients with adult respiratory distress syndrome. Role of cytokine production. 141 30

In order to ascertain the role of TNF-alpha in pulmonary tuberculosis, we determined the TNF-alpha productivity of alveolar macrophages(AMs) obtained by bronchoalveolar lavage(BAL), along with the level of TNF-alpha in the serum of patients with tuberculosis including pulmonary, miliary, and endobronchial tuberculosis, healthy controls, and pulmonary diseases such as diffuse interstitial lung disease (DILD) and pneumonia. AMs from patients with pulmonary tuberculosis did not produce a larger amount of TNF-alpha than did those from the healthy control subjects. However, among the patients with pulmonary tuberculosis, the AMs from the fresh and reactivated groups produced a larger amount of TNF-alpha than those from the inactive group. AMs from patients showing positivity in culture produced a larger amount of TNF-alpha than those showing negativity. The average level of serum TNF-alpha in patients with pulmonary tuberculosis was slightly higher than that of the healthy control group. Among patients with pulmonary tuberculosis, significantly increased levels of serum TNF-alpha were noted in the reactivated group compared to those of the fresh and inactive group. Patients with moderate to far-advanced infiltration on their chest X-rays, showed a significantly higher level of serum TNF-alpha than those with minimal involvement on the chest X-ray. Smokers from the healthy control group showed a significantly higher level of serum TNF-alpha than non-smokers from the same group. These results suggest that an increase in the production of TNF-alpha may correspond with the severity of pulmonary tuberculosis.
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PMID:Production of tumor necrosis factor-alpha by alveolar macrophages from patients with pulmonary tuberculosis. 188 49

Eosinophils (EOs) participate in a variety of inflammatory states characterized by endothelial cell damage, such as vasculitis, pneumonitis, and endocarditis. We find that 100 U/ml TNF-alpha/cachectin (TNF), a concentration attainable in the blood of humans with parasitic infestations, stimulates highly purified populations of EOs to damage human umbilical vein endothelial cells (HUVEC), a model of human endothelium. This TNF-dependent EO cytotoxicity is strongly inhibited by heparin and methyprednisolone but unaffected by the platelet-activating factor antagonist BN52012 or scavengers of superoxide anion and H2O2, superoxide dismutase and catalase. However, addition of a physiologically relevant concentration of Br- (100 microM) enhances EO/TNF damage to HUVEC, implicating the possible participation of EO peroxidase (EPO) in the killing mechanism. EOs adherent to FCS-coated plastic wells more than double their production of superoxide anion and the cytotoxic EPO-derived oxidant HOBr when exposed to TNF, showing that TNF activates the respiratory burst of EOs attached to a "physiologic" surface. Unlike PMNs, EOs were not irreversibly activated to kill unopsonized endothelium by previous exposure to TNF, and did not degranulate or upregulate CR3 expression as detected by Mo1 in the presence of 100 U/ml TNF. HUVEC exposed 18 h to TNF were considerably more susceptible to lysis by PMA-activated EOs and reagent H2O2, demonstrating a direct effect of TNF upon endothelium, perhaps through inhibition of antioxidant defenses. These findings suggest that abnormally elevated serum levels of TNF may provoke EOs to damage endothelial cells and thereby play a role in the pathogenesis of tissue damage in hypereosinophilic states.
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PMID:Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. 197 79

Alveolar macrophages (AMS) initiate inflammation during Pneumocystis carinii pneumonia by releasing cytokines including TNF-alpha. Recent studies suggest that macrophage responses to P. carinii are enhanced by serum opsonization, but the mechanisms of enhancement are not well defined. To determine whether macrophage release of TNF-alpha in response to P. carinii was augmented by immune opsonization, alveolar macrophages obtained from rabbits were cultured with P. carinii that had been opsonized with either nonimmune rabbit serum, immune serum generated against P. carinii, or an affinity-purified polyclonal Ab recognizing the major P. carinii surface Ag gp120. Each experiment also included organisms maintained in media alone (nonopsonized P. carinii). Opsonization of P. carinii with immune serum or gp120 Ab significantly enhanced macrophage TNF-alpha release. Interestingly, however, opsonization with nonimmune serum also increased TNF-alpha response to the organism. Because P. carinii is known to interact with the adhesive glycoproteins, vitronectin (VN) and fibronectin (FN), we hypothesized that they might also augment TNF-alpha release. Opsonization of P. carinii with VN or FN resulted in significant potentiation of macrophage TNF-alpha liberation. We further determined that VN and FN were present in increased quantities in the lower respiratory tract of patients with P. carinii pneumonia compared with normal volunteers. Additionally, VN and FN were demonstrated on the surface of freshly isolated P. carinii organisms by immunoblot analysis. Our study suggests that immune and nonimmune opsonins contribute to host defenses during P. carinii pneumonia by enhancing regional TNF-alpha release in response to the organism.
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PMID:Vitronectin, fibronectin, and gp120 antibody enhance macrophage release of TNF-alpha in response to Pneumocystis carinii. 751 99

The activation of autologous cytotoxic cells by interleukin-2 (IL-2) may be a promising tool for elimination of minimal residual blast populations in patients with acute myelocytic leukemia (AML) to prolong disease-free survival. Here, we report the results of a phase II study using IL-2 for consolidation therapy in patients with second remission of de novo AML. All patients in 1st relapse of AML received a uniform induction therapy consisting of intermediate high-dose AraC (iHDAraC) 2 x 600 mg/m2 d1-4 and VP-16 100 mg/m2 d1-7. Patients achieving 2nd remission were treated with 4 cycles recombinant IL-2 (rIL-2) 9 x 10(6) IU/m2 administered on d1-5 and 8-12/cycle as 1h infusion every six weeks. In 37/66 (56%) evaluable patients, complete remission (CR) was achieved. So far, 21/37 patients (4 after additional autologous bone marrow transplantation (ABMT) received rIL-2 consolidation. Three patients are too early for evaluation, 4 received allogeneic BMT, 6 relapsed before IL-2 was scheduled and 4 refused treatment with rIL-2. The median disease-free survival (DFS) was 11 (4-49+) months. Up to now, in 5/21 (24%) patients the duration of 2nd remission exceeded that of 1st remission 7/21 (33%) are in ongoing 2nd remission (7+ to 49+ months). The side effects of rIL-2 were generally moderate and manageable. Only in two patients, previously treated with ABMT, severe side effects occurred; septicaemia and pneumonia in one patient and desquamative erythrodermia in the second one. In accordance with other studies rebound lymphocytosis with a marked increase of CD56(+)-cells and release of secondary cytokines such as TNF-alpha, IFN-gamma and IL-6 was observed. The schedule is feasible and the data suggest a possible benefit for DFS, which, however has to be confirmed by randomized trials.
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PMID:Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myeloblastic leukemia. 771 35

A chlamydial-specific T cell clone, capable of inhibiting the growth of infectious Chlamydia in vivo and in vitro, was employed to investigate the effect of gamma-irradiation on the ability of effector T cells to control infections. Clone 2.14-0 (CD4+), specific for the Chlamydia trachomatis biovar agent of mouse pneumonitis (MoPn), was irradiated with varying doses (0, 2.5, 5.0, 10.0, 20.0 and 40.0 Gy) and its biological functions and ability to inhibit the intraepithelial growth of MoPn were assessed. The results revealed that although gamma-irradiation drastically reduced the proliferative response of the clone to antigen, it did not affect the phenotype and the effector function of inhibiting chlamydial growth. The preservation of anti-chlamydial function after gamma-irradiation correlated with the retention of IFN-gamma and TNF-alpha secretion in response to antigenic stimulation. We conclude that the biologic functions of T cells requiring proliferation and differentiation are more likely to be adversely affected by gamma-irradiation on the short-term, but the effector functions, possibly associated with cytokines and cytolysis, may be preserved among persisting effector T cells in an irradiated individual.
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PMID:Effect of gamma-irradiation on the effector function of T lymphocytes in microbial control. 777 31

Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM-1, levels of soluble ICAM-1 (sICAM-1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM-1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM-1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM-1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM-1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM-1 and the factors IgG-RF, IgM-RF, erythrocyte sedimentation rate (ESR) and TNF-alpha in sera of RA patients. In addition, it was noted that the levels of sICAM-1 in SF were as high as those in the sera of patients with RA.
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PMID:Soluble intercellular adhesion molecule-1 (ICAM-1) antigen in patients with rheumatoid arthritis. 790 95

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.
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PMID:Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. 792 34

Pneumonia is one of the major sites of infection in ventilated newborns. We investigated whether the cytokines IL-1 beta and TNF-alpha are detectable in tracheal aspirates of newborns with pneumonia as a diagnostic marker. All 12 infants with pneumonia had elevated levels of IL-1 beta (range 30-300 pg/ml) and TNF-alpha (range 60-680 pg/ml), whereas control infants (n = 21; respiratory distress syndrome, very low birth weight or infants intubated preoperatively) had no detectable levels of IL-1 beta or TNF-alpha. In vitro investigations with mononuclear cells of umbilical cord blood were performed to rule out that exogenously added surfactant influences IL-1 beta and TNF-alpha production. It is concluded that IL-1 beta and TNF-alpha are important and specific mediators of neonatal pneumonia which may be of diagnostic importance.
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PMID:Increased levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in tracheal aspirates of newborns with pneumonia. 800 82


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