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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mononuclear cells of the lamina propria (LpMNC), isolated from endoscopically taken biopsies of the large bowel from AIDS patients, were analysed for their ability to secrete tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6. Stimulation of LpMNC from normal controls with pokeweed mitogen (PWM) led to a time- and dose-dependent enhancement of TNF-alpha, IL-1 beta and IL-6 secretion. In contrast, PWM stimulation of LpMNC from AIDS patients resulted in only a small increase in TNF-alpha release. Constitutive secretion of IL-1 beta and IL-6 in these patients was already increased to the concentration range of stimulated cells from normal controls and could not be further increased, probably due to maximal in vivo stimulation. Secretion of TNF-alpha, IL-1 beta and IL-6 by peripheral blood monocytes (PBM) and alveolar macrophages from AIDS patients was elevated with or without stimulation compared with normal controls. Obviously, the regulation of TNF-alpha secretion is dependent on the microenvironment. Since it is known that interferon-gamma (IFN-gamma) may induce the production of TNF-alpha, the secretion of this cytokine was examined. Release of IFN-gamma was constitutively and under stimulation lowered in LpMNC from AIDS patients compared with normal controls. Addition of IFN-gamma to LpMNC did not result in enhanced TNF-alpha secretion. Our data indicate a defective function of intestinal mononuclear cells in AIDS patients as shown by the diminished TNF-alpha secretion.
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PMID:Differences in cytokine secretion by intestinal mononuclear cells, peripheral blood monocytes and alveolar macrophages from HIV-infected patients. 841 83

Mycobacterium avium is an intracellular pathogen that causes disseminated infection in patients with AIDS. Colonial morphotype (smooth-transparent (SmT) vs smooth-domed (SmD)) is a key determinant of virulence in mice and the capacity for replication in human monocytes. Some cytokines (IL-1 and IL-6) promote, whereas others (IFN-gamma and TNF) inhibit intracellular M. avium growth. The specific factors that determine virulence of M. avium, however, are not clear. In this study, we examined cytokine expression by human monocytes stimulated with isogeneic cloned isolates of M. avium. Monocytes were prepared from healthy donors and cultured with or without isogeneic M. avium for up to 7 days. Cytokine levels (IL-1, IL-6, and TNF-alpha) in monocyte supernatants and cell lysates were measured by immunoassay using an ELISA. The expression of cytokine mRNA by monocytes infected with M. avium also was determined by extracting total RNA and subjecting it to Northern blot analysis. Optimal cytokine release occurred at 24 h. SmD induced higher levels of the following cytokines in supernatants than SmT: IL-1 alpha (140 +/- 32 (mean +/- SE) vs 47 +/- 16 pg/ml, p < 0.02), IL-1 beta (4.0 +/- 0.9 vs 1.7 +/- 0.5 ng/ml, p < 0.01), and TNF-alpha (2725 +/- 546 vs 1464 +/- 409 pg/ml, p < 0.01). IL-6 production was comparable for both strains. SmD and SmT isolates induced comparable levels of steady state mRNA for IL-1 beta, TNF, and IL-6. Pulse-chase analysis indicated that differences in cytokine expression between SmT and SmD occurred in monocyte lysates at the earliest time point (immediately after pulse-labeling). The dissociation of the expression of specific mRNA from production of IL-1 and TNF suggests that translational capacity for the expression of certain cytokines was reduced by the more virulent SmT. Differential induction of cytokine may be a factor in the pathogenicity of M. avium strains isolated from patients with AIDS.
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PMID:Colonial morphotype as a determinant of cytokine expression by human monocytes infected with Mycobacterium avium. 845 66

The pathogenesis of the dementia associated with human immunodeficiency virus (HIV) infection is unclear, but has been postulated to be due to indirect effects of HIV infection including the local production of cytokines. To determine which cytokines are produced in the nervous system and to identify any correlations with dementia, cytokine and HIV messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction in the brains from 24 HIV-infected patients with and without dementia and 9 HIV-uninfected control subjects. Levels of tumor necrosis factor-alpha messenger RNA were significantly higher and levels of interleukin (IL)-4 messenger RNA were significantly lower in demented compared to nondemented HIV-infected patients. Demented patients also had lower IL-1 beta levels than did nondemented patients. No significant differences were detected in the amounts of leukemia inhibitory factor, IL-6, transforming growth factor-beta 1 and -beta 2, monokine induced by gamma interferon-2 (MIG-2), or interferon-gamma messenger RNAs. IL-10 and IL-2 messenger RNAs were undetectable in all brains examined. Cytokine messenger RNA levels in nondemented HIV-positive patients were similar to those in HIV-negative control subjects. HIV transcripts were more abundant in subcortical white matter than in the basal ganglia, cortex, or deep white matter. Our findings suggest a possible role for tumor necrosis factor-alpha in the development of neurological dysfunction. Increased levels of tumor necrosis factor-alpha messenger RNA were not associated with increased levels of IL-1 beta messenger RNA, suggesting differential regulation of these monokines in acquired immunodeficiency syndrome dementia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. 849 37

Polymorphonuclear granulocytes (PMN; or neutrophils) from uninfected or human immunodeficiency virus-infected subjects were tested for their ability to inhibit growth of Candida albicans and produce interleukin-1 beta (IL-1 beta) and IL-6 in vitro. It was seen that PMN from AIDS (Centers for Disease Control stage IV) patients expressed equal if not greater anticandidal activity compared with the activity expressed by neutrophils from all other subjects examined. On exposure to granulocyte macrophage-colony-stimulating factor or to a mannoprotein constituent (MP-F2) from C. albicans itself, PMN from AIDS patients showed enhanced antifungal activity and production of remarkable quantities of IL-1 beta and IL-6. These findings suggest that the functional abilities of PMN to inhibit Candida growth and secrete relevant proinflammatory and immunomodulatory cytokines are intrinsically preserved in AIDS patients.
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PMID:Anticandidal activity and interleukin-1 beta and interleukin-6 production by polymorphonuclear leukocytes are preserved in subjects with AIDS. 850 Dec 41

Most studies of apoptosis on T lymphocytes have examined the effects of various stimuli on immature T cells from the thymus. Previous work has indicated that apoptosis of mature memory T cells may be an important pathophysiologic mechanism in diseases such as AIDS, cancer, and autoimmunity. The effect of IL-2 on apoptosis of T cells is not clear. Therefore, we studied the ability of IL-2 to rescue Ag-specific T cells from apoptosis. We found that IL-2, in a dose-dependent manner, prevented T cells from entering apoptosis induced by gamma-irradiation, mitomycin C, or dexamethasone. This effect was specific for IL-2; IL-1 beta, IL-6, or IFN-gamma could not reproduce it. In contrast to Ag-specific T cells, immature T cells and naive mature peripheral T cells could not be rescued by IL-2 from radiation-induced apoptosis. Apoptosis rescue by IL-2 was associated with the induction of bcl-2 mRNA and protein. This induction could not be attributed to the effects of IL-2 on the cell cycle, as T cells that were prevented from cell cycle progression by irradiation showed a similar induction of bcl-2. Rescued cells retained their Ag-specific proliferative capacity and in vivo functions. These findings demonstrate that the apoptotic death of Ag-specific T cell lines, cells which can be regarded as a model for memory T cells, can be prevented with IL-2. This effect may have important therapeutic implications for patients receiving chemotherapy or radiotherapy, and for patients with AIDS who develop immunodeficiency primarily as a result of loss of Ag-specific memory T cells.
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PMID:IL-2 rescues antigen-specific T cells from radiation or dexamethasone-induced apoptosis. Correlation with induction of Bcl-2. 854 1

Elevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS. Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR. In THP-1 cells, Fc gamma R cross-linking induced NF-kappa B, which is known to bind to the regulatory region of the long terminal repeat (LTR) of HIV-1 and to activate HIV-1 transcription. Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1-LTR-driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking. These results indicate that Fc gamma R can mediate a TNF-alpha-dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes.
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PMID:Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat-driven transcription in human monocytes. 856 12

Microglia are the major target for human immunodeficiency virus (HIV) infection within the central nervous system. Because only a few cells are productively infected, it has been suggested that an aberrant cytokine production by this cell population may be an indirect mechanism leading to the development of neurological disorders in HIV-infected patients. Therefore we decided to study the secretion pattern of several interleukins (IL) by microglial cells and peripheral blood macrophages isolated from uninfected and simian immunodeficiency virus (SIV)-infected Rhesus monkeys. We found that uninfected, unstimulated primate microglia produce more IL-6 and less TNF alpha than peripheral blood macrophages, but generate comparable levels of IL-1 beta and IL-8. After infection with SIV in vitro, synthesis of all cytokines tested is increased compared to uninfected cultures and to peripheral blood macrophages. Microglia isolated from infected animals produce more IL-8 and TNF alpha than the uninfected cultures and display a strongly increased capacity to secrete TNF alpha upon stimulation with lipopolysaccharide. In addition, production of IL-6 by in vivo-infected microglia increases with time in culture to very high levels despite the fact that only a few cells contained replicating virus. These findings clearly show that the cytokine production of microglia is impaired after SIV infection both in vitro and in vivo and that a low level of viral replication is sufficient for these alterations to occur. In conclusion, the results of this study further support a possible role of cytokines in the pathogenesis of neuro-AIDS.
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PMID:The effect of simian immunodeficiency virus infection in vitro and in vivo on the cytokine production of isolated microglia and peripheral macrophages from rhesus monkey. 866 83

Among immunological abnormalities present in human immunodeficiency virus type 1 (HIV-1)-infected individuals are dysregulation of cytokine production and CD4 down-regulation in both T-helper cells and monocytes/macrophages. The HIV-1 envelope glycoprotein 120 (gp120) has the ability to induce different cytokines in peripheral blood mononuclear cells and in monocytes/macrophages in vitro which in some instances have been reported to down-regulate macrophage CD4 expression. This study provides evidence that HIV-1 recombinant gp120 (rgp120) down-regulates both surface and total CD4 expression in primary tissue culture-differentiated macrophages (TCDM) at the level of transcription. The CD4 down-regulation observed in TCDM occurred between 6 and 12 hr after rgp120 treatment preceded by a peak of endogenous tumour necrosis factor-alpha (TNF-alpha) observed at 3-6 hr post-treatment. We demonstrate that the TCDM CD4 down-regulation observed after rgp120 treatment was inhibited by the use of an anti-huTNF-alpha monoclonal antibody (mAb), but not by mAb directed against other cytokines induced by rgp120, such as interleukin-1 beta (IL-1 beta) and interferon-alpha (IFN-alpha). The present findings roughly parallel those observed both in the sera of patients and in the monocytes/macrophages isolated from HIV-positive individuals, suggesting that gp120 by stimulating endogenous TNF-alpha production could be a good candidate for the CD4 down-regulation observed in the monocytes/macrophages of HIV-1-infected individuals. In contrast to CD4 down-regulation in HIV-infected lymphocytes, which results from a direct effect of viral genes on CD4 expression, soluble factors such as cytokines induced during HIV infection might explain the monocyte/macrophage CD4 dysregulation observed in acquired immune deficiency syndrome.
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PMID:HIV-1 envelope glycoprotein gp120 down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor-alpha. 870 50

In adult multicellular organisms, homeostasis is determined in each cell lineage by a balance between cell death and cell growth. Dysregulation of cell death mechanisms is involved in the pathogenesis of an increasing number of diseases. Defective apoptosis can participate in malignant transformation, viral latency and autoimmune diseases. Excessive apoptotic cell death is involved in CD4+ T-cell depletion observed in acquired immune deficiency syndrome, in fulminant hepatitis associated with infection by hepatitis B and C viruses, in some neurodegenerative disorders and haematological diseases, in polycystic kidney disease and ischaemia. Three steps can be distinguished in the pathway that leads to cell death. The first step involves interactions between the extracellular and intracellular signals that decide whether a cell should live or die. When death is chosen, a common pathway that involves at least the Bcl-2- family of proteins and the interleukin-1 beta (IL-1 beta)-converting enzyme-related cysteine proteases confirms whether or not the cell should die. Finally, if death is allowed to occur, the apoptotic process itself is characterized by deoxyribonucleic acid (DNA) fragmentation, proteolysis and morphological changes that precede the engulfment of apoptotic cells by neighbouring cells and phagocytes. Several inducers and inhibitors of apoptosis acting on one or several of these three steps that characterize the apoptotic process have been identified in vitro. Their potential usefulness in improving the current therapeutic strategies and designing new strategies in several different diseases is discussed.
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PMID:The role of apoptosis in the pathogenesis and treatment of diseases. 880 51

HIV infection ultimately leads to AIDS, despite the immune responses elicited soon after infection. In addition to the observed changes in lymphoid cell subsets, alteration of the cytokine network most likely accompanies and/or contributes to the lack of protective immune responses. In an attempt to delineate the early events in the immune response to lentivirus infection, we have sequentially monitored levels of proinflammatory (IL-1 beta, IL-6, and TNF-alpha) and antiinflammatory (IL-10) cytokine mRNAs in PBMCs of cynomolgus macaques during primary SIVmac infection. Eight monkeys were infected i.v. with 4 AID50 of cell-free SIVmac251. All monkeys seroconverted between days 16 and 21 postinfection (p.i.), and had detectable peripheral viremia. The viral load peaked between days 12 and 16 p.i., and fell sharply thereafter. A marked increase in the expression of IL-6 mRNA was observed in all macaques during the first weeks following infection. An increase in the levels of expression of IL-1 beta, TNF-alpha, and IL-10 mRNA was also determined in six, six, and five of the eight monkeys, respectively. While IL-6, TNF-alpha, and IL-10 increased transiently, increased levels of IL-1 beta mRNA expression were sustained over 44 days in most monkeys.
AIDS Res Hum Retroviruses 1996 Feb 10
PMID:Interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, and interleukin 10 responses in peripheral blood mononuclear cells of cynomolgus macaques during acute infection with SIVmac251. 883 3


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