Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:017444 (TNF)
 61,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetes mellitus (DM) show an increased susceptibility to bacterial infections due to the presence of neutrophil dysfunction. Susceptibility to tuberculosis has also been reported in such patients, however, the reason remains unclear. This study measured the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) by the peripheral monocytes of patients diagnosed with pulmonary tuberculosis accompanied by DM (TB+DM) and patients without DM complications (TB) using age-matched, healthy control subjects for comparison. Also examined was the relationship between cytokine production and DM control. The results were as follows: (1) The production of IL-1 beta, TNF alpha and IL-6 in TB patients was significantly higher than that observed in the healthy control subjects. (2) The production of IL-1 beta, TNF alpha and IL-6 in TB+DM patients was significantly lower than that observed in the TB patients. (3) The production of IL-1 beta and TNF alpha in TB+DM patients with poor control was significantly lower than that observed in the patients with good control. (4) The TNF alpha production had a significant inverse correlation to HbA1c in the TB+DM patients. This study demonstrated that the production of cytokines is impaired in TB+DM patients and suggests a close correlation between tuberculosis immunity and DM.
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PMID:[Case study of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 production peripheral blood monocytes in patients with diabetes mellitus complicated by pulmonary tuberculosis]. 129 80

Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by macrophages, which has been shown to cause endothelial cell damage, pyrexia and weight loss, clinical features of tuberculosis, but not of sarcoidosis which is in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma interferon, factors which are present in vivo in both tuberculosis and sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho-alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic) disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid from any of the groups. PAMs from control patients released no detectable TNF spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was not increased further by addition of an optimal concentration of LPS. Thus, the pulmonary macrophages of patients with sarcoidosis and tuberculosis released significantly more TNF than those of controls.
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PMID:Tumour necrosis factor production by alveolar macrophages in pulmonary sarcoidosis and tuberculosis. 134 39

Tissue sites involved in certain types of inflammation become sensitive to the destructive effect of a subsequent injection of tumour necrosis factor alpha (TNF alpha). To try to further delineate the cascade of effector and regulatory events controlling this activity, a new model is described and its main properties characterized. C57BL/GrFa mice received mycobacterial products subcutaneously in the footpads. Recombinant TNF alpha was injected 24 h later into the same sites. To assess the tissue-destructive effect of TNF alpha in these "primed" footpads, swelling and haemoglobin content of injected footpads were measured, 16 h and 20 h respectively after the injection of TNF alpha. When loaded with either Escherichia coli LPS (10 micrograms) or Mycobacterium vaccae soluble sonicate (17 micrograms), footpads were reactive to the subsequent injection of 1 microgram recombinant TNF alpha, as assessed by both swelling and haemoglobin content. When C57BL/GrFa mice received 10(9) autoclaved M. vaccae subcutaneously in the back 10 days before the footpad was "primed" with soluble M. vaccae sonicate, the destructive effect of TNF alpha was significantly enhanced, becoming 5-10-fold greater than that seen in sites "primed" with an optimal dose of LPS. This higher reactivity was abrogated by a single dose of anti-CD4 given just before the injection of TNF alpha. This local reactivity to TNF alpha of skin sites loaded with mycobacterial products is compared to the local LPS-dependent Shwartzman reaction, and the relevance of this assay as a model with which to delineate the mechanisms of tissue damage in tuberculosis is discussed.
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PMID:TNF alpha-mediated tissue damage in mouse footpads primed with mycobacterial preparations. 136 Jun 90

The quantitative relationships among the in vitro lymphocyte proliferation in peripheral blood in 19 healthy donors to purified protein derivative (PPD) and the killed Mycobacterium tuberculosis, interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) production in these culture supernatants, and the in vivo skin reaction to PPD which were simultaneously measured were studied. Statistical analysis was performed with t-test and multiple regression analysis: The results obtained were as follows; 1) The magnitude of the in vitro lymphocyte proliferation by PPD and the killed M. tuberculosis failed to correlate with the erythema and the induration of the in vivo skin reaction to PPD. 2) The erythema of skin test correlates with TNF alpha production in the culture supernatants that the lymphocytes in peripheral blood were cocultured with these antigens for 7 days. (R = 0.566062, 0.01 less than p less than 0.02) 3) There is a correlation between the erythema and the induration of skin test. (R = 0.526662, 0.02 less than p less than 0.05). 4) Though the magnitude of the lymphocyte proliferation to PPD correlates IFN gamma production in the culture supernatants (R = 0.525915, 0.02 less than p less than 0.05), these response to the killed M. tuberculosis correlates both IFN gamma production (R = 0.55049, 0.01 less than p less than 0.02) and TNF alpha production (R = 0.51283, 0.02 less than p less than 0.05) in the culture supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Correlation of tuberculin skin reaction with lymphocyte proliferation, interferon-gamma production and tumor necrosis factor-alpha production after in vitro stimulation with PPD and killed Mycobacterium tuberculosis using peripheral blood of healthy donors]. 143 16

The marriage of two scourges, one old (mycobacterial disease) and one new (HIV), has presented an enormous challenge to the medical and public health communities, and has stirred renewed interest in mechanisms for immune control of mycobacterial infection. Virulence of both M. avium and M. tuberculosis appears to be inversely related to the capacity of the microorganisms to induce production of protective cytokines in infected hosts. TNF alpha and IFN gamma are central to this process, and mycobacterial polysaccharides may be their main determinant. Despite these similarities, M. tuberculosis and M. avium cause illnesses at the polar extremes of HIV disease. Tuberculosis, occurring early in the course of HIV disease, may promote HIV replication in otherwise latently infected cells via induction of cytokines. As such, the potential exists for accelerated progression to AIDS due to the mutual synergy of these pathogens.
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PMID:Macrophages, mycobacteria and HIV: the role of cytokines in determining mycobacterial virulence and regulating viral replication. 145 67

Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia.
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PMID:Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. 162 1

The activated macrophages present in the T cell-dependent granulomata of sarcoidosis and tuberculosis are primed for enhanced release of cytokines including tumour necrosis factor (TNF or cachectin). Release of this cytokine can induce an acute-phase response, fever, and necrosis in suitably prepared sites of inflammation; if chronic, its presence may contribute to weight loss. These clinical features are characteristic of tuberculosis, but not of sarcoidosis, though alveolar macrophages from both diseases release large quantities of TNF in vitro. We therefore postulated the presence in sarcoidosis patients of an inhibitor of TNF. We have studied levels of TNF inhibitory activity by determining the quantity of TNF required to give 50% kill of L929 cells in the presence of 20% heat-inactivated serum derived from various disease states (37 sarcoidosis, 13 tuberculosis, 13 Crohn's disease, 17 healthy donors). Normal sera used in this way do not inhibit significantly, but inhibition of TNF toxicity is caused by most sera from both sarcoidosis and tuberculosis. Used at 20%, five out of 37 sarcoidosis sera and one out of 13 tuberculosis sera caused complete inhibition of TNF, even when the latter was added at 100 times the concentration required to give 50% kill in control wells. This inhibitor may have an important physiological role.
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PMID:An inhibitor of the toxicity of tumour necrosis factor in the serum of patients with sarcoidosis, tuberculosis and Crohn's disease. 169 61

TNF and IFN-gamma are thought to be involved in the immune response to mycobacterial infection because they exhibit antimycobacterial effects in vitro. To investigate the roles of these cytokines in vivo at the site of disease activity in human tuberculosis, we evaluated local cytokine production in patients with tuberculous pleuritis. Both TNF and IFN-gamma were selectively concentrated 5- to 30-fold in pleural fluid, compared to blood of the same patients. Messenger RNA for both cytokines was detected in pleural tissue by in situ hybridization, suggesting that selective cytokine concentration is due to local cytokine production. Two Mycobacterium tuberculosis cell wall components, the protein-peptidoglycan complex and lipoarabinomannan, caused dose-dependent release of TNF by pleural fluid mononuclear cells and may constitute the stimuli for TNF production in the pleural space. In contrast to results obtained for TNF release, the protein-peptidoglycan complex, but not lipoarabinomannan, stimulated IFN-gamma release by pleural fluid mononuclear cells. The clinical manifestations of tuberculous pleuritis, such as fever, exudative pleural effusion, and tissue necrosis, may be due to the effects of elevated local TNF concentrations, produced in response to mycobacterial cell wall components.
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PMID:Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis. 211 53

Tumor-necrosis-factor-alpha (TNF-alpha), which is secreted by cells of the macrophage/phagocytic system, interact in a variety of different ways with other cytokines and immunologically active substances. To investigate a possible role of TNF-alpha in granulomatous lung diseases and to determine whether sarcoidosis can be differentiated from tuberculosis on the basis of serum TNF-alpha levels, we studied sera from patients with sarcoidosis and active tuberculosis. Ninety-one percent of the patients with sarcoidosis and 83% of the patients with tuberculosis exhibited significantly elevated TNF-alpha levels as compered with controls. Since these levels remained elevated irrespective of clinical stage and even under therapy, it is believed that patients with sarcoidosis and tuberculosis experience continuous activation of TNF-2-alpha-producing cells of the myelomonocytic system. In addition, determination of serum TNF-alpha levels does not permit differentiation between sarcoidosis, tuberculosis or malignant disease.
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PMID:[Alpha tumor necrosis factor in the serum of patients with sarcoidosis, tuberculosis or bronchial cancer]. 216 37

We still do not understand the mechanism of immunity ty mycobacteria in man, and convincing reproducible kill of M. tuberculosis by human macrophages has not been achieved. The pathways so far elucidated, involving gamma interferon, 1,25(OH)2 vitamin D3, and TNF release seem more likely to lead to immunopathology than to protection. Meanwhile the major problem for the clinician is the existence of "persister" bacteria, which are not eliminated by the immune response, even when therapy has greatly reduced the bacterial load. It seems unlikely that it will be possible to design antibiotics which will rapidly kill dormant persister bacilli, so new strategies for therapy may need to concentrate on modulation of the host response. The objectives of such therapies would be: 1) "Reawakening" of dormant persisters. 2) Rapid immune recognition of persisters. 3) Suppression of the tissue-damaging pathway. 4) Enhancement of the optimally protective mechanism, but this has not yet been defined.
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PMID:Mycobacteria, cytokines and antibiotics. 219 23


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