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)

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

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

At 4 wk after intraperitoneal inoculation of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable only in the salivary glands. When T cells of these mice were activated by a single injection of anti-CD3 epsilon monoclonal antibody, mice died of interstitial pneumonitis at 24-48 h after injection, accompanied by elevation of serum levels of TNF-alpha and IFN-gamma. However, MCMV remained undetectable in the lungs during the period. Simultaneous injection of cyclosporin A reduced such effects of anti-CD3. In conclusion, although the presence of MCMV in the host may be required, MCMV-associated pneumonitis is not mediated by virus in the lung but probably by the cytokines released from T cells, of which responsiveness to stimulation via CD3 molecule has been presumably modified by MCMV infection.
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PMID:Murine cytomegalovirus-associated pneumonitis in the lungs free of the virus. 808 43

Adult varicella can be a severe illness complicated by pneumonia, encephalitis, or prolonged fever. This study measured levels of tumor necrosis factor (TNF)-alpha, interleukin-2 (IL-2), and interferon gamma (IFN-G) in a consecutive group of 31 adult varicella patients presenting within 24 hours of rash onset. All cytokines were assayed using an ELISA technique. TNF-alpha was detectable in 71% of patients with a mean level of 52 pg/ml. IL-2 was detectable in 29% with a mean level of 1040 pg/ml. IFN-gamma was detectable in only 9%. There was no correlation between TNF, IL-2, or IFN-G level and clinical severity as determined by duration and severity of cutaneous findings, duration of fever, frequency of hepatitis, or thrombocytopenia.
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PMID:Tumor necrosis factor, interleukin-2, and interferon-gamma in adult varicella. 808 51

Acute lung injury, characterized as the adult respiratory distress syndrome (ARDS), is a common clinical occurrence following blood loss and injury. We previously found increased levels of transforming growth factor (TGF)-beta 1 mRNA in murine intraparenchymal mononuclear cells and in alveolar macrophages within 1 h after hemorrhage. Because TGF-beta has potent proinflammatory and immunoregulatory properties, we investigated the effect of blocking TGF-beta with mAb on hemorrhage-induced pathology, cytokine mRNA levels in lungs, as well as survival from pneumonia. Mice treated with anti-TGF-beta mAb showed normal pulmonary histology 3 days after hemorrhage and resuscitation in contrast to the mononuclear and neutrophil infiltrates, intraalveolar hemorrhage, and interstitial edema found in hemorrhaged mice either treated with control antibody or not treated with any antibody. Decreased mRNA levels for IL-1 beta, TNF-alpha, IL-6, IL-10, and IFN-gamma as compared with untreated, hemorrhaged controls were present in intraparenchymal pulmonary mononuclear cells following therapy with anti-TGF-beta. In contrast, therapy with anti-TGF-beta increased mRNA levels for IL-1 beta and TNF-alpha in alveolar macrophages and for TGF-beta in peripheral blood mononuclear cells collected 3 days after hemorrhage. Administration of anti-TGF-beta to hemorrhaged mice did not correct the enhanced susceptibility to Pseudomonas aeruginosa pneumonia that exists after hemorrhage. These results suggest that TGF-beta has an important role in hemorrhage-induced acute lung injury, but does not contribute to the post-hemorrhage depression in pulmonary antibacterial response.
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PMID:Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice. 808 71

SIVsmmPBJ 1.9 is an extremely virulent clone of the simian immunodeficiency virus SIVsmmPBj 14 that causes an acute lethal disease in pigtail macaques, with death occurring 6 to 8 days after infection. The disease is characterized by bloody mucoid diarrhea, lymphoid hyperplasia, and giant cell pneumonia. We have developed an in vitro model for the production of multinucleated giant cells (MGCs) in which peripheral blood monocytes rapidly fuse to form MGCs when cultured in lymphocyte-conditioned medium and antibody against class II MHC. We have tested the effect of SIVsmmPBj on monocytes in our MGC model system. Peripheral blood mononuclear cells (PBMCs) from normal healthy human subjects, when cultured in the presence of anti-class II MHC monoclonal antibody and SIVsmmPBj 1.9, but not either alone, resulted in the formation of MGCs within 4 days. Experiments using Transwell chambers indicated that such MGCs are formed by fusion of monocytes, not by virus-induced fusion of lymphocytes. SIVsmmPBj 1.9 is unique in inducing MGC formation in that other SIV and HIV isolates do not induce MGCs. Whereas SIVsmmPBj 1.9 grown in PBMCs was a potent inducer of MGCs in the presence of anti-class II MHC antibody, SIVsmmPBj 1.9 grown in CEMx174 failed to do so. Antibodies against IFN-gamma and TNF-alpha significantly inhibited SIVsmmPBj/anti-class II-induced formation of MGCs. These results indicate that cytokines released in response to SIVsmmPBj 1.9, in conjunction with antibodies to class II MHC, caused fusion of monocytes.
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PMID:Simian immunodeficiency virus SIVsmmPBj 1.9 induces multinucleated giant cell formation in human peripheral blood monocytes. 817 65

Host defense against murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) in a murine model was investigated. Gamma interferon (IFN-gamma) was produced in the lungs by both MoPn-susceptible nude athymic (nu/nu) and MoPn-resistant heterozygous (nu/+) mice. In vivo depletion of IFN-gamma in nu/nu mice led to exacerbation of infection. Fluorescence-activated cell sorter analysis disclosed induction of GL3 antibody-positive cells (putatively gamma/delta+ T cells) in nu/nu mouse lung during infection with MoPn. Treatment of nu/nu mice in vivo with antibody to NK cells (anti-asialo GM1 antibody) or to gamma/delta cells (UC7-13D5) did not significantly decrease IFN-gamma production in the lung. However, treatment of severe combined immunodeficiency mice (which lack gamma/delta cells) with antibody to NK cells significantly reduced lung IFN-gamma levels.
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PMID:Gamma interferon levels during Chlamydia trachomatis pneumonia in mice. 833 89

The patterns of cytokine mRNA expression in mice with primary or secondary influenza pneumonia have been assessed by in situ hybridization analysis of cells from both the mediastinal lymph node (MLN) and the virus-infected lung. Evidence of substantial transcriptional activity was found in all lymphocyte subsets recovered from both anatomical sites. The kinetics of cytokine mRNA expression after primary infection with an H3N2 virus were in accord with the idea that the initial response occurs in regional lymphoid tissue, with the effector T cells later moving to the lung. This temporal separation was much less apparent for the more rapid secondary response resulting from challenge of H3N2-primed mice with an H1N1 virus. Among the T cell receptor alpha/beta+ subsets, transcripts for interferon (IFN) gamma and tumor necrosis factor beta were most commonly found in the CD8+ population whereas mRNA for interleukin (IL) 4 and IL-10 was much more prevalent in CD4+ T cells. The gamma/delta T cells expressed mRNA for all cytokines tested, with IL-2, IL-4, and IFN-gamma predominating among those recovered from the inflammatory exudate. At particular time points, especially early in the MLN and late in the infected lung, the frequency of mRNA+ lymphocytes was much higher than would be expected from current understanding of the prevalence of virus-specific precursors and effectors. If this response is typical, induction of cytokine gene expression for T cells that are not responding directly to the invading pathogen may be a prominent feature of acute virus infections.
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PMID:Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. 842 16

Rhodococcus equi, and intracellular respiratory pathogen, causes sever e granulomatous pneumonia in humans with AIDS and in young horses. Pulmonary clearance of R. equi requires functional CD4+ T cells and gamma interferon (IFN-gamma) expression from bronchial lymph node cells. The purpose of this study was to investigate whether R. equi-specific CD4+ Th1 cells could effect clearance of R. equi from the lung. Adoptive transfer of a clearance of R. equi from the lungs. In contrast, mice transfused with a R. equi-specific CD4+ Th2 cell line expressed interleukin-4 but not IFN-gamma mRNA, failed to clear pulmonary infection, and developed granulomas in the lung. Control mice, which did not receive cells, did not produce IFN-gamma or interleukin-4 and developed small pulmonary granulomas. These results clearly show that a Th1 response is sufficient to effect pulmonary clearance of R. equi.
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PMID:Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung. 860 68


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