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 current study examined the proliferative capacity and cytokine secretion pattern of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus type 1 (HIV-1)-infected patients in response to the major surface glycoprotein (MSG) of Pneumocystis carinii. PBMC from AIDS patients with <200 CD4 cells/mL had significantly less proliferative responses to MSG than did healthy controls. Cytokine analysis indicated that interferon-gamma secreted in response to MSG was also significantly less. There was no significant difference in interleukin-4 levels following incubation with MSG between any of the groups; however, all the HIV-infected persons had slightly elevated levels. When the CDC class C3 patients who had a previous episode of P. carinii pneumonia were compared with those who had not had a previous episode, there was a significant increase in the proliferative response to MSG and in interleukin-4 secretion. CDC class C3 patients who had a previous episode of P. carinii pneumonia showed a predominately Th2 response to MSG.
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PMID:Proliferative and cytokine responses of human T lymphocytes isolated from human immunodeficiency virus-infected patients to the major surface glycoprotein of Pneumocystis carinii. 941 98

This study was undertaken to determine if recombinant interferon-gamma (rIFN-gamma) given every other day as maintenance therapy could prolong the survival of patients with small cell lung cancer (SCLC) who achieved a complete or nearly-complete response to induction therapy. A secondary endpoint was to assess the toxicity of alternate day doses of this treatment. One hundred and seventy seven patients in complete or nearly-complete response following chemotherapy with or without thoracic radiotherapy were studied. Patients were randomised to receive either rIFN-gamma 4 million units (0.2 mg) subcutaneously every other day for 4 months or observation. One hundred and twenty of the 127 registered patients were eligible; 59 patients received IFN and 61 patients without maintenance therapy were followed. Alternate day IFN was reasonably well tolerated by the majority of patients, but in 12% substantial non-haematological toxicity (including flu-like syndrome) occurred. One of 3 patients with pneumonitis died after having received 3.6 mg IFN. The median survival time from the date of randomisation was 8.9 months for the IFN arm and 9.9 months for the observation arm. rIFN-gamma at the dose and schedule used in this study failed to prolong response duration and survival in SCLC patients in complete or nearly-complete response. The toxicity seen with every other day doses of IFN was less than that reported with daily dosing. The hypothesis that this agent may increase the deleterious effects of radiation on normal lung tissue was supported by the development of pneumonitis in 3 cases of whom 1 had a fatal outcome. The results do not warrant further studies with rIFN-gamma on maintaining response in SCLC.
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PMID:Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC Lung Cancer Cooperative Group. 989 43

Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.
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PMID:Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice. 951 2

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In the early phase of infection, macrophages and polymorphonuclear cells (PMN) are the first immune cells that interact with GBS. In this in vitro study, to gain insight into GBS-macrophage interaction in the absence of type-specific antibodies, we examined the features of GBS survival in thioglycollate-elicited murine peritoneal macrophages and the effect of GBS on the protein kinase C (PKC)-dependent transduction pathway. Our results demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH 31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly in macrophages for up to 24 and 48 hr, respectively. However, macrophage activation by interferon-gamma (IFN-gamma) and lipopolysaccharide from Escherichia coli (LPS) caused a significant reduction in the time of intracellular persistence. Macrophage activation by IFN-gamma and LPS seems to be a multifactorial event involving multiple intracellular signal pathways also including PKC. Since PKC is one of the components in the signal network leading to macrophage activation and an important target for several intracellular micro-organisms, we wondered whether PKC could have a role in intracellular GBS survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate (PMA) for 18 hr and PKC inhibition by Calphostin C rendered macrophages more permissive for the intracellular GBS survival. Furthermore, GBS-infected macrophages were unable to respond to PMA and LPS, activators of PKC, by inducing antimicrobial activity. The ability of GBS to impair PKC-dependent cell signalling was also demonstrated by the reduced c-fos gene expression in GBS-infected macrophages with respect to control macrophages, after LPS stimulation. In conclusion, our results indicate that GBS survive in macrophages and impairment of PKC signal transduction contributes to their intracellular survival.
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PMID:Group B streptococci persist inside macrophages. 953 23

A lymph node biopsy sample from a boy aged with fever, pneumonia, hepatosplenomegaly, lymphadenopathy and pancytopenia, showed histiocytosis with erythrophagocytosis, compatible with the haemophagocytic syndrome. Treatment consisted of dexamethasone and etoposide, with cyclosporine added in a later phase. During the subsequent remission phase, bone marrow transplantation was carried out. Haemophagocytic syndrome is a rare condition, characterized by fever, pancytopenia, hepatosplenomegaly and characteristic laboratory findings (including a high interferon-gamma level) and morbid-anatomical findings (haemophagocytic histiocytic cells in bone marrow, lymph nodes, liver and spleen, but also in the CNS, kidneys and lungs). Recent pathophysiological discoveries indicate an enhanced T-cell response, leading to hypercytokinaemia. As a rule the patient dies from multiorgan failure and diffuse intravascular coagulation. Bone marrow transplantation is the treatment of choice.
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PMID:[Hemophagocytic syndrome]. 955 Jul 48

The aim of the present study was to further characterize the role of alveolar macrophages (AM) in acute human lung inflammation by evaluating their capacity to produce pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Patients with severe community-acquired pneumonia (CAP; n=12) and healthy volunteers (n=10) underwent bronchoalveolar lavage (BAL). AM were separated to high purity (>96%) using fluorescence-activated cell sorting. We determined the TNF-alpha, IL-6 and IL-8 cytokine gene expression in AM ex vivo using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Moreover, we measured in vitro unstimulated, lipopolysaccharide (LPS)- and LPS/interferon-gamma inducible TNF-alpha, IL-6 and IL-8 cytokine release and evaluated samples of BAL fluids for the same pro-inflammatory cytokines using an enzyme-linked immunosorbent assay (ELISA). We found increased TNF-alpha, IL-6 and IL-8 messenger ribonucleic acid (mRNA) levels in AM from CAP patients that were significantly elevated only for IL-8. When challenged with endotoxin in vitro, AM obtained from CAP patients showed a strongly reduced potential to release TNF-alpha and IL-6 compared to healthy controls, whereas IL-8 secretion did not differ significantly between groups. Moreover, stimulation of AM from CAP patients with LPS plus IFN-gamma augmented TNF-alpha and IL-6 cytokine release to near normal levels. Interestingly, no TNF-alpha protein was measured in BAL samples from CAP patients, whereas IL-6 and IL-8 protein levels were found to be significantly increased. Together, highly purified alveolar macrophages from community-acquired pneumonia patients show relatively low ex vivo tumour necrosis factor-alpha and interleukin-6 but not interleukin-8 messenger ribonucleic acid levels that are associated with a decreased pro-inflammatory cytokine release in vitro which, however, can be restored by concurrent interferon-gamma stimulation.
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PMID:Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. 959 98

Virus-specific CD8+ effector T cells (eCTL) are enriched in the lungs of mice with primary influenza pneumonia, though later detection of memory T cells (mCTL) in the mediastinal lymph nodes (MLN) or spleen by peptide-based staining protocols is at the limits of flow cytometric analysis. Respiratory challenge with an H3N2 virus months after H1N1 priming induces a massive recall response, which reduces virus titers 2-3 days earlier than in nave controls. Influenza-specific mCTL produce interferon-gamma within 6 hr, but still take 4-5 days to localize to the infected respiratory tract. The delay reflects that the recall response develops first in the MLN, which contains relatively few mCTL. The response to a subdominant epitope is less obvious after secondary challenge.
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PMID:Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. 965 82

The serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured by enzyme immunoassays in 44 patients with Chlamydia (n = 13) or Mycoplasma (n = 14) pneumonia or influenza A infection (n = 17) and in 20 control subjects. The levels of IFN-gamma were raised in 29/44 patients. The concentrations of IL-6 were raised in 32/44 patients. Raised levels of TNF-alpha were seen in 26/44 but there was no significant difference between the levels of the different groups of patients. All three cytokines indicated clinical recovery when acute and convalescent samples from 10 patients with Chlamydia pneumonia were analyzed. IFN-gamma, IL6 and TNF-alpha are present in the circulation in the majority of patients with Chlamydia and Mycoplasma pneumonia and in influenza A infection. We suggest that repeated measurement of cytokines, such as IL-6, IFN-gamma and TNF-alpha, may be useful in the management of lower respiratory tract infections but further studies are needed to define the value of cytokine measurements in acute pneumonia.
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PMID:Cytokine responses in patients with pneumonia caused by Chlamydia or Mycoplasma. 973 Jul 97

Using gene knockout and wild-type C57BL/6 mice, we examined the role of alpha beta and gamma delta T cells in the resolution of Chlamydia trachomatis mouse pneumonitis (MoPn) biovar pulmonary infection. The results show that alpha beta T-cell-deficient (alpha-/-) mice, when compared with wild-type control mice, have dramatically increased mortality rate and greater in vivo growth of MoPn. The alpha beta T-cell-deficient mice were as susceptible to MoPn infection as T- and B-lymphocyte-deficient (RAG-1-/-) mice. Moreover, both alpha beta T-cell-deficient and RAG-1 mutant mice failed to mount delayed-type hypersensitivity (DTH) responses to organism-specific challenge and showed undetectable interferon-gamma (IFN-gamma) production by spleen cells upon in vitro organism-specific restimulation. In contrast, gamma delta T-cell-deficient mice exhibited intact DTH responses and their mortality rate and in vivo chlamydial growth were comparable to those in wild-type controls. More interestingly, gamma delta T-cell-deficient mice showed significantly higher levels of IFN-gamma production than did wild-type mice. The data indicate that the alpha beta T cell is the major T-cell population for acquired immunity to chlamydial infection and that gamma delta T cells may play an ancillary role in regulating the magnitude of alpha beta T-cell responses.
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PMID:Different roles are played by alpha beta and gamma delta T cells in acquired immunity to Chlamydia trachomatis pulmonary infection. 976 33

Resistance to Pneumocystis carinii is achieved through cell-mediated and humoral immunity, but the interplay between these two systems in the immunocompetent host is not fully understood. TCRbetaxdelta-/- double-mutant mice deficient of all T cell populations naturally acquired P. carinii pneumonia with lethal consequences. Moribund mutants displayed numbers of pulmonary pathogens comparable to RAG-1-/- mice lacking all functional T and B lymphocytes. Pulmonary lavage cells of diseased TCRbetaxdelta-/- mutants secreted proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-12, and interferon-gamma, but not IL-4, -5, or -10. Serum immunoglobulin levels of both healthy and diseased mice were significantly reduced compared with immunocompetent animals. Secreted antibodies were mainly IgM, which also bound P. carinii. Mutants completely lacked IgG1, emphasizing strict T cell dependence of immunoglobulin switching to this isotype. Other IgG subclasses were strongly reduced and did not bind P. carinii. These results suggest that T cells are crucial for generation of antibodies against P. carinii relevant to resistance.
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PMID:Pneumocystis carinii pneumonia in mutant mice deficient in both TCRalphabeta and TCRgammadelta cells: cytokine and antibody responses. 987 31


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