Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0026918 (Mycobacterium)
52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tuberculous meningitis (TBM) is a devastating form of tuberculosis that occurs predominantly in children and in immunocompromised adults. To study the pathogenesis of TBM, a rabbit model of acute mycobacterial central nervous system infection was set up (8-day study). Inoculation of live Mycobacterium bovis Ravenel intracisternally induced leukocytosis (predominantly mononuclear cells), high protein levels, and release of tumor necrosis factor-alpha (TNF-alpha) into the cerebrospinal fluid within 1 day. Histologically, severe meningitis with thickening of the leptomeninges, prominent vasculitis, and encephalitis was apparent, and mortality was 75% by day 8. In animals treated with antituberculous antibiotics only, the inflammation and lesions of the brain persisted despite a decrease in mycobacteria; 50% of the rabbits died. When thalidomide treatment was combined with antibiotics, there was a marked reduction in TNF-alpha levels, leukocytosis, and brain pathology. With this combination treatment, 100% of the infected rabbits survived, suggesting a potential clinical use for thalidomide in TBM.
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PMID:A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death. 960 34

The cytopathic effect of HIV on CD4 T cells, as well as the active autoimmune mechanism occurring during infection, have been documented. Of the cytokines involved in the pathogenesis of AIDS, the main one produced by the monocyte-macrophage series is tumor necrosis factor alfa (TNF alpha). This cytokine induces antigens such as proteinase 3 (Pr 3) or mieloperoxidase (MPO). Anti-neutrophil cytoplasmic antibodies (ANCA) are directed against this type of PMN antigens. In the present paper, the role of anti-neutrophil cytoplasmic antibodies (ANCA) in HIV infected patients as responsible for autoimmune phenomena in relation to opportunistic infections, was studied. A total of 88 serum samples belonging to 49 asymptomatic and 39 symptomatic HIV infected patients were tested for ANCA by an indirect immunofluorescence (IIF) test over a neutrophil substrate. ANCA were detected in 53.8% of symptomatic patients as compared to 4.1% in asymptomatic cases (p < 0.0001). A 95.9% correlation was observed between ANCA-positive samples and pulmonary infection (n = 20). In those ANCA (+) samples 95.9% correlation was found with pulmonary infection (n = 20). Pulmonary infection due to Mycobacterium tuberculosis is a frequent finding in HIV infected patients from Northeastern Argentina. When the presence of ANCA in TB(+) HIV(+) and TB(+) HIV(-) patients was studied, it was seen that positive-ANCA significantly correlated with the first group (p < 0.001). The presence of ANCA was not related to viral infections, toxoplasmosis, neurological features of AIDS, vasculitis or malignant diseases. ANCA during pulmonary infection, mostly caused by TB, as well as PMN infiltration in pulmonary parenchyma, and the deregulated immune reaction elicited by HIV, may contribute to the onset of autoimmune phenomena. The presence of human T lymphocytes reactive to heat stress proteins (Hsp), an important target of immune response against certain intracellular auto-antigens such as MPO from PMN, added to the mechanism of molecular mimicry, could explain the association of ANCA and TB in patients with severe alterations of their immune response. According to these results, the limited presence of ANCA in asymptomatic patients HIV(+) and in HIV(-) with pulmonar TB, could indicate that the virus may not be responsible for the induction of these antibodies.
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PMID:[Anti-neutrophil cytoplasmic antibodies (ANCA) in patients with symptomatic and asymptomatic HIV infection]. 964 Jul 62

To elucidate the role of neutrophils in the early inflammatory response to mycobacterial infection, expression of chemokines interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) was examined in human blood neutrophils in response to the lipopolysaccharide (LPS) of Escherichia coli, which induces acute inflammation, or to Mycobacterium tuberculosis or purified protein derivative (PPD), which induce chronic mycobacterial inflammation. Neutrophils stimulated with LPS, M. tuberculosis, or PPD expressed both IL-8 and MIP-1alpha. Expression of IL-8 and MIP-1alpha was lower after stimulation with M. tuberculosis or PPD than after stimulation with LPS, but the kinetics of expression did not differ significantly. In contrast, both M. tuberculosis and PPD with tumor necrosis factor-alpha induced neutrophils to undergo rapid cell death, which might remove neutrophils and activate macrophages at sites of mycobacterial inflammation. The findings suggest that neutrophils play important roles in the host defense against mycobacterial infection.
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PMID:Expression of chemokines and induction of rapid cell death in human blood neutrophils by Mycobacterium tuberculosis. 965 32

Protective immunity against Mycobacterium tuberculosis (MTB) in animal models is based on cell-mediated immunity (CMI), involving bi-directional interactions between T cells and cells of the monocyte/macrophage (MO/MA) lineage. Key factors include MO-derived interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha as well as T cell derived IL-2 and interferon (IFN)-gamma. These cytokines appear particularly crucial in the induction of MA-mediated elimination of mycobacteria. Several lines of evidence indicate that similar mechanisms are operating in humans. During active pulmonary tuberculosis (PTB), signs of both immune depression and immune activation are concomitantly present. Decreased tuberculin skin test reactivity in vivo and deficient IFN-gamma production by MTB-stimulated mononuclear cells in vitro are observed. On the other hand, the serum levels of several cytokines, including TNF, and other inflammatory mediators are increased and circulating MO and T cell show phenotypic and functional evidence of in vivo activation. In this review, we will discuss the evidence for three models, which could explain this apparent paradox: 1. Stimulation of the T cell-suppressive function from MO/MA; 2. Intrinsic T cell refractoriness, possibly associated with tendency to apoptosis (programmed cell death), and 3. Compartmentalization and redistribution of immune responses to the site of disease. The opportunistic behavior of MTB during human immunodeficiency virus (HIV) infection can be explained by suppression of type-1 responses at the level of antigen-presenting cells, CD4 T cells and effector macrophages. The ominous prognostic significance of intercurrent PTB during HIV infection seems primarily due to prolonged activation of HIV replication in macrophages. Supportive immune therapy during PTB could aim at correcting the type-1 deficiency either by IFN-gamma inducers (e.g. IL-12, IL-18) or by neutralizing the suppressive cytokines transforming growth factor beta (TGF-beta) and IL-10. Alternatively, inflammatory over-activity could be reduced by neutralizing TNF. Finally, anti-apoptotic therapies (e.g. IL-15) might be considered.
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PMID:Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and suppression/anergy. 971 47

Interferon-alpha (IFN-alpha) is a cytokine exerting pleiotropic activities, including antimicrobial effects, especially directed against intracellular infectious bacteria. It may be administered by aerosol to reach the lower respiratory tract without systemic side effects. The aim of the study reported here was the evaluation of aerosolized IFN-alpha treatment (3 MU/dose, given three times a week; total study dose: 72 MU/2 mo) in combination with conventional antimycobacterial therapy in patients with pulmonary tuberculosis. Two groups of 10 patients each were compared before and after 2 mo of conventional antituberculous chemotherapy with or without inhaled IFN-alpha. Several biologic (bronchoalveolar lavage fluid [BALF] cellularity, Mycobacterium tuberculosis [MT] number in sputum), biochemical (BALF concentrations of 10 cytokines, BALF IFN-alpha receptor levels), and clinical (fever, vital signs, high-resolution computed tomography [HRCT] images) measures were made in these patients at the time of their enrollment and at the end of the observation period of the study. Fever, MT number in sputum, and abnormalities in HRCT images showed significantly earlier resolution in the IFN-alpha-treated group, together with a more significant decrease in BALF interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) concentrations and significantly greater pre- versus posttreatment variations in IL-2 and IFN-gamma. These data, taken together, suggest that IFN-alpha administration may favorably affect the evolution of pulmonary tuberculosis when combined with antimycobacterial therapy.
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PMID:Effects of aerosolized interferon-alpha in patients with pulmonary tuberculosis. 976 75

Regulation of interleukin (IL)-12 production by coexpression of tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor (TGF)-beta in human monocytes infected with Mycobacterium tuberculosis H37Ra was analyzed. Also, since IL-12 induces interferon (IFN)-gamma, the effect of IFN-gamma on IL-12 expression was examined. IL-12 mRNA was measured by reverse transcriptase-polymerase chain reaction and IL-12 protein by ELISA. IL-12 p35 mRNA was constitutive and inducible. IL-12 p70 protein paralleled IL-12 p40 protein expression. TNF-alpha protein expression occurred earlier than IL-12 p40 protein but was not required for IL-12 induction. Addition or neutralization of TGF-beta did not significantly alter IL-12 induction. In contrast, recombinant IL-10 reduced IL-12 and neutralization of IL-10 minimally enhanced IL-12. A pronounced increase in IL-12 followed IFN-gamma pretreatment, which selectively up-regulated IL-12 p35 mRNA. Further understanding of operative cytokine networks during M. tuberculosis infection may improve strategies for vaccine development and immunotherapy.
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PMID:Regulation of interleukin-12 by interleukin-10, transforming growth factor-beta, tumor necrosis factor-alpha, and interferon-gamma in human monocytes infected with Mycobacterium tuberculosis H37Ra. 980 41

Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. This microorganism is capable of inducing a delayed hypersensitivity reaction in the lung, with subsequent expression of the disease. This reaction depends on the presence of different cytokines that exert specific functions. The aim of this study was to evaluate the presence and the concentrations of nine different modulators in bronchoalveolar lavage fluid (BALF). For this purpose, 15 patients with active pulmonary tuberculosis were enrolled at the time of diagnosis, prior to institution of antituberculous therapy. All the patients demonstrated M. tuberculosis in the sputum, and their disease extention was defined by high-resolution computed tomography (HRCT) using a score which included the presence of six findings: miliary nodules, nodules < 10 mm, consolidation, ground glass, cavity and bronchial wall thickening. This score was more sensitive than an equivalent score calculated on the basis of chest radiology. HRCT score was calculated for each area of the two lungs in order to define the more and the less affected lung for each patient. The bronchoalveolar lavage (BAL) was performed in the more affected area for each lung. The HRCT total score for each washed area ranged between 1 and 15, and showed more significant differences between the more and less affected lungs (p = 0.0004) than those obtained with the individual radiologic findings (p ranged between 0.60 and 0. 004). The BAL concentrations of the nine cytokines evaluated for the more and less affected lungs were compared: interleukin-6 (IL-6), IL-8, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) showed significant differences (p ranged between 0. 016 and 0.0007). In addition, each cytokine concentration was correlated with the HRCT score. Significant correlations were found with IL-12, IL-6, IL-8, IL-2, and TNF-alpha. The correlations between cytokines and HRCT total score were better than those observed with the individual radiologic findings. A correlation matrix for the different cytokines evaluated one against each other, has also been added to show common behavior of these modulators. A similar analysis was also performed for the radiologic abnormalities.
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PMID:Cytokine levels correlate with a radiologic score in active pulmonary tuberculosis. 987 32

CRL-1072 is a poloxamer surfactant that kills mycobacteria more effectively within macrophages than in broth cultures. Human macrophages treated with CRL-1072 synthesized interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in a dose-dependent manner. About 3000 pg of IL-8 per million human macrophages accumulated in cultures treated with 100-1500 ng of poloxamer, with mRNA message for IL-8 induced as early as 2 h. As macrophages do not have IL-RA receptors, a transwell culture was used to study the chemotactic and activating effects of IL-8 between CRL-1072-treated human macrophage effectors and polymorphonuclear neutrophil (PMN) targets. PMN were activated by IL-8 and secreted hydrogen peroxide and myeloperoxidase (MPO). MPO derived from PMN, in turn, activated monocytes for an enhanced killing of intracellular Mycobacterium avium. The ability of CRL-1072 to modulate macrophage-mediated activation of neutrophils and receive a feedback activation signal may form one mechanism by which its antimycobacterial activity is achieved in vivo.
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PMID:CRL-1072 enhances antimycobacterial activity of human macrophages through interleukin-8. 1004 70

Bone marrow-derived macrophages (BMM) comprise a population of quiescent cells which can be activated by defined signals. Here, we directly compare the release of chemokines and monokines by BMM raised either in serum-supplemented or in serum-free medium in response to Listeria monocytogenes EGD or Mycobacterium bovis BCG infection. We focused on this issue because there have been several controversial reports on the production of cytokines by BMM due to different in vitro culture conditions. Culture in serum-supplemented medium primed BMM for release of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-12, but had no effect on macrophage inflammatory protein (MIP)-1alpha and tumor necrosis factor (TNF)-alpha production in response to L. monocytogenes infection. After challenge infection with M. bovis, BMM raised and stimulated in serum-supplemented medium secreted higher levels of MCP-1, MIP-1alpha, IL-6, and TNF-alpha but not of IL-12 as compared to BMM cultured and infected in a serum-free medium. The effects of serum could be partially mimicked by interferon-gamma. Because the serum components responsible for BMM priming are undefined, BMM cultured under serum-free conditions provide an appropriate cell population for defining macrophage activating signals.
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PMID:Effect of fetal calf serum on cytokine release by bone marrow-derived macrophages during infection with intracellular bacteria. 1008

To determine whether the extent of spread of Mycobacterium tuberculosis strains in the community correlated with their capacity to replicate in human macrophages, intracellular growth rates of M. tuberculosis patient isolates were measured. Strain 210 caused disease in 43 patients in central Los Angeles, 3 "small-cluster" strains caused disease in 8-23 patients, and 5 "unique" strains each caused disease in only 1 patient who was positive by sputum acid-fast smear and spent substantial amounts of time at homeless shelters that were tuberculosis transmission sites. Strain 210 isolates grew significantly more rapidly than small-cluster and unique strains in macrophages. All strains elicited production of similar amounts of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and IL-12 and were equally susceptible to reactive nitrogen intermediates. It was concluded that the extensive spread of an M. tuberculosis strain correlated with its capacity to replicate rapidly in human macrophages, which may be a marker of virulence.
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PMID:Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in human macrophages. 1019 Dec 25


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