Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using three-colour flow cytometry, we have measured intracellular IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) induced in human CD4+ and CD8+ T cells from normal donors and patients with common variable immunodeficiency (CVID). Since a new range of directly FITC-conjugated anti-cytokine antibodies was used, conditions were optimized for the concentration of antibody, for cell permeabilization and fixation, and for the time of exposure to monensin to retain the cytokines within the cell. Kinetics of intracellular cytokine production were measured for up to 20 h in culture with phorbol myristate acetate (PMA) and ionomycin, or with phytohaemagglutinin (PHA). Kinetic studies of activation with PMA and ionomycin show that a higher proportion of normal CD4+ cells can make IL-2 than the other two cytokines, and that there are more TNF-alpha-positive CD4+ cells than cells with IFN-gamma. For normal CD8+ cells the highest production of cytokine is of IFN-gamma (up to 50% of the cells) especially at longer times (10-20 h) of stimulation. For CD8+ cells, IL-2-positive cells exceed those with TNF-alpha. The other mitogenic stimulus used (PHA) was grossly inferior to PMA and ionomycin in its ability to induce intracellular cytokines. The time of exposure to monensin was also examined. Its continuous presence in the cultures (up to a maximum of 20 h) increased the detection of IL-2-positive cells without apparently reducing the percentage of cytokine-positive CD4+ or CD8+ cells. Finally, using optimal conditions, we compared cytokine production in cells from patients with the disease CVID and showed normal cellular levels of ability to produce IL-2 and TNF-alpha but significantly raised levels of production of IFN-gamma in both CD4+ and CD8+ lymphocytes. This suggests that the pathology of this disease may involve an excessive Th1-type response.
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PMID:Intracellular cytokine production by human CD4+ and CD8+ T cells from normal and immunodeficient donors using directly conjugated anti-cytokine antibodies and three-colour flow cytometry. 880 43

We studied lumbosacral dorsal root ganglia (DRGs) from 10 patients with acquired immunodeficiency syndrome (AIDS) and five controls using immunocytochemistry, in situ hybridization and NADPH-diaphorase (NADPHd) histochemistry. Human immunodeficiency virus (HIV)-1 RNA was detected in five AIDS cases, and HIV-1 p24 antigen was found in four of these patients. The densities of nodules of Nageotte (nN), macrophages and major histocompatibility complex-class II-positive cells were significantly increased in the DRGs of AIDS patients compared to controls. Cytomegalovirus antigen was observed in the DRGs of four AIDS cases and one control, but without its presence being related to neuronal degeneration. Furthermore, we detected tumor necrosis factor, interferon-gamma, interleukin (IL)-1 beta, and IL-6 in the DRGs from AIDS patients. Using NADPHd histochemistry, we showed that the number of NADPHd-positive neurons was significantly increased in the DRGs of AIDS patients compared to controls, implying upregulation of nitric-oxide (NO) production in AIDS DRGs. Generally, there were increased numbers of nN in DRGs which contained more NADPHd-positive neurons. Additionally, immunoreactivity for an inducible form of NO synthase was detected in interstitial cells in AIDS DRGs. These results suggest that reactive inflammation, including the production of cytokines, occurs in the DRGs of AIDS patients and that excessive production of NO may be related to neuronal degeneration in AIDS DRGs.
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PMID:Increased NADPH-diaphorase reactivity and cytokine expression in dorsal root ganglia in acquired immunodeficiency syndrome. 881 58

Human immunodeficiency virus (HIV) infection is associated with increased concentrations of neopterin derivatives, released in large quantities by human macrophages on stimulation with interferon-gamma (INF-gamma). Neopterin concentrations thus inversely correlate with absolute CD4+ T-cell numbers and strongly predict progression of disease from latency to AIDS. Investigations of hydrogen peroxide-induced chemiluminescence indicated a potential role of neopterin and 7,8-dihydroneopterin in oxygen free radical-mediated processes. Indeed, 7,8-dihydroneopterin is able to enhance tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, accompanied by an increased production of reactive oxygen intermediates (ROIs). In line with this finding, the same combination appears to contribute to the upregulation of HIV replication due to activation of nuclear factor-kappa B (NF-kappa B), a central enhancer element of the HIV LTR promoter. Thus, besides the role of neopterin as sensitive indicator of disease activity in HIV infection, neopterin derivatives apparently are associated with the cascade of events that regulate the HIV production in infected individuals.
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PMID:Role of neopterin and 7,8-dihydroneopterin in human immunodeficiency virus infection: marker for disease progression and pathogenic link. 886 84

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity by facilitating type 1 helper T-lymphocyte responses, enhancing the lytic activity of natural killer cells, augmenting specific cytolytic T-lymphocyte responses, and inducing the secretion of interferon-gamma. It can also boost the production of some subclasses of IgG antibodies. IL-12 has demonstrated activity in several mouse models of infectious diseases caused by viruses, protozoans, fungi, and mycobacteria. It has the potential for use either as a single immunotherapeutic agent, in combination with chemotherapeutic agents, or as a vaccine adjuvant. Endogenous IL-12 appears to play an important role in the host defence against intracellular pathogens; poor IL-12 production observed in mononuclear cells from patients infected with the human immunodeficiency virus may be involved in the susceptibility of this patient group to opportunistic infections. Clinical trials are being initiated to evaluate the possible therapeutic uses of IL-12.
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PMID:Interleukin-12: potential clinical applications in the treatment and prevention of infectious diseases. 886 32

The consequences of complexing an antigen with specific antibodies upon the antigen-induced immune response were studied with respect to secretion of interleukin-2 (IL2), interleukin-6 (IL6), interleukin-10 (IL10) and interferon-gamma (IFN gamma). We found that the tetanus toxoid antigen-induced cytokine pattern was mainly dependent on the antigen/antibody ratio. While tetanus toxoid antigen alone induced a typical Th1-like cytokine pattern with high levels of IL2 and IFN gamma, equivalent or antibody-excess immune complexes induced a marked secretion of IL6 and IL10 while failing to induce IL2 and IFN gamma secretion. As the cytokine pattern plays a crucial role in the development of specific immune responses towards infectious agents, our results indicate that immune complexes--typically occurring during the course of chronic infectious diseases--may play an important role in the modulation of immune responses. Since a shift from Th1 to Th2 immune responses has been discussed as a pathogenetic factor in HIV-induced immunodeficiency, the role of circulating immune complexes as a possible cause for this shift should be considered.
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PMID:Distinct antigen-induced cytokine pattern upon stimulation with antibody-complexed antigen consistent with a Th1-->Th2-shift. 890 28

T cells depend on costimulation by accessory cells for an immune response. Costimulatory macrophage activity involves the expression of B7 molecules whose expression is upregulated by interferon-gamma (IFN-gamma) and downregulated by interleukin-10 (IL-10). The expression of low-affinity Fc gamma IIIR (CD16), in contrast, is upregulated in the presence of IL-10 and downregulated in the presence of IFN-gamma. In human immunodeficiency virus-1 (HIV-1) infection, the balance between IFN-gamma and IL-10 expression shifts toward IL-10 predominance. Herein, we compare B7 and CD16 macrophage phenotypes from healthy and from HIV-1-infected patients. Patient macrophages express B7 molecules in lower density than macrophages from healthy donors and are resistant to the upregulation of costimulatory molecule expression. B7 expression can be normalized in patient macrophages by treating them with anti IL-10 monoclonal antibodies (mAb) and IFN-gamma together but not by treatment with either anti-IL-10 mAb or IFN-gamma alone. This finding suggests an excess of IL-10 in HIV-1 infection and an IFN-gamma deficiency, consistent with previous cytokine assessments in HIV-1-infected subjects. The upregulation of CD16 expression was readily induced in patient macrophages by treatment with IL-10 and was inhibited by treatment with IFN-gamma. CD16 expression identifies the subset of cytotoxic macrophages that has been shown to destroy CD4T cells, which they target through CD4-reactive immune-complexed HIV-1 envelope molecules.
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PMID:The cell surface marker phenotype of macrophages from HIV-1-infected subjects reflects an IL-10-Enriched and IFN-gamma-deprived donor environment. 893 73

Activation of human blood neutrophils and monocytes for enhanced release of toxic oxygen radicals may take place after priming with several cytokines including hematopoietic growth factors. The potential impact of human immunodeficiency virus (HIV) on this response and the relative potency of various cytokines remains unclear. Blood neutrophils and monocytes were isolated from 25 HIV outpatients with variable immunodeficiency. Oxidative burst response upon stimulation with N-formyl-methionyl-leucyl-phenylalanine was assessed in neutrophils after priming with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-g), and in monocytes after priming with GM-CSF and IFN-g. Monocyte oxidative burst responses were not changed in patients or controls. In contrast, following priming with IFN-g, GM-CSF or medium (but not G-CSF) the neutrophils in HIV patients with CD4 counts > 200 x 10(9)/L exhibited a significantly higher chemiluminescence response than was seen in healthy age-matched controls, whereas the response in patients with lower CD4 counts was not different from controls. At comparable concentrations, GM-CSF induced a significantly higher priming than G-CSF and IFN-g. A significant positive correlation between CD4 counts and priming activity of GM-CSF and IFN-g on neutrophils was observed. We conclude that neutrophils in HIV infection have a normal or enhanced response to the oxidative metabolism priming activity of hematopoietic growth factors in vitro, whereas priming effect on monocytes was not seen.
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PMID:Priming of neutrophil and monocyte activation in human immunodeficiency virus infection. Comparison of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interferon-gamma. 897 88

The level of interferon-gamma (IFN-gamma) in pleural fluid has been reported to be increased in pleural tuberculosis. Nevertheless, its diagnostic value has not yet been well-established, and immunocompromised patients have not previously been evaluated. The aim of this study was to determine the value of the IFN-gamma level in pleural fluid for diagnosing tuberculous pleurisy in immunocompetent and immunocompromised patients. Three hundred and eighty eight consecutive patients were studied prospectively (73 with tuberculous pleural effusions, including nine with concurrent human immunodeficiency virus (HIV) infection and one after liver transplantation, and 315 with nontuberculous effusions). IFN-gamma was measured by radioimmunoassay. The sensitivity of the test, using a 3.7 U.mL-1 cut-off point, was 0.99 (95% confidence interval (95% CI) 0.93-1.00) and the specificity was 0.98 (95% CI 0.96-1.00). The sensitivity of the test did not differ in HIV-positive and HIV-negative patients. Patients with lymphoma, vasculitis or vascular connective tissue disease did not have abnormal IFN-gamma values. In conclusion, the level of interferon-gamma in pleural fluid is a very good diagnostic marker of tuberculous pleural effusion, even in immunocompromised patients.
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PMID:Interferon-gamma in 388 immunocompromised and immunocompetent patients for diagnosing pleural tuberculosis. 898 Sep 81

The role of interleukin-12 (IL-12) in Th1 cell differentiation is well established. The heterodimer p70, composed of a p40 and a p35 chain, is the biologically active form. IL-12 production by human monocytes is enhanced by interferon-gamma (IFN-gamma) and inhibited by IL-10 and prostaglandin E2 (PGE2). Peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected individuals reportedly have impaired IL-12 p40 and p70 production on stimulation with Staphylococcus aureus Cowan I (SAC) in vitro. Both PGE2 and IL-10 previously were proposed to be instrumental in this defect in IL-12 production. Here, we studied IL-12 p40 and p70 production in relation to IL-10 and PGE2 production in whole blood cultures from HIV-infected individuals. On stimulation with lipopolysaccharide, IL-12 production was normal. However, on stimulation with SAC, IL-12 p40 and p70 production was decreased in HIV-infected individuals and correlated significantly with decreased peripheral blood CD4+ T-cell number and T-cell reactivity to CD3 monoclonal antibody in vitro. However, IL-10 and PGE2 production in cultures from HIV-infected individuals was normal and did not relate to IL-12 production. In conclusion, IL-12 production by cells from HIV-infected individuals is impaired under certain conditions in vitro and this decrease is independent of IL-10 or PGE2 production.
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PMID:Interleukin-12 (IL-12) production in whole blood cultures from human immunodeficiency virus-infected individuals studied in relation to IL-10 and prostaglandin E2 production. 900 60

Limited information is available about the pathogenesis of acquired immune deficiency syndrome (AIDS)-associated idiopathic interstitial pneumonitis, a common noninfectious complication of human immunodeficiency virus (HIV) infection. Infection of C57B1/6 mice with LP-BM5 retrovirus, a murine model of AIDS, leads to development of a diffuse interstitial pneumonitis that displays many features of human AIDS-associated interstitial pneumonitis. To further characterize the cellular and molecular features of this lung disease, the temporal development of cellular infiltration, cytokine expression, and virus replication were evaluated in lung tissue of virus-infected mice. Persistent expression of viral RNA was detectable in lungs as early as 1 wk after infection. Infiltration of the lungs by CD4+ and CD8+ T cells, by IgG+ and IgA+ B cells, and by macrophages was observed by 4 wk after infection and continued through 8 wk of infection. Histologically, cellular infiltration was most pronounced in peribronchial and perivascular regions, whereas inflammation of alveolar septae and alveolar spaces was minimal. In contrast to normals, T cells from infected lungs were immunodeficient in that they failed to proliferate in response to the mitogen concanavalin A (ConA). However, evaluation of cytokine mRNA expression by interstitial lung lymphoid cells indicated that cells from infected lungs were chronically activated, in that elevated expression of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) was observed throughout the course of infection. Similarly, expression by interstitial lung lymphoid cells of mRNA for the proinflammatory cytokine IL-1 and the fibrogenic cytokine transforming growth factor-beta (TGF-beta) was also increased following infection. These results indicate that retrovirus-induced immunodeficiency in mice is associated with infiltration and chronic activation of lymphoid cells in the lungs. Furthermore, simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests that cytokine-expressing cells in infected lungs may be unresponsive to inhibitory and antiinflammatory effects of IL-10 and/or TGF-beta, thus contributing to chronicity of inflammation in this disorder.
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PMID:Pulmonary lymphoid cell activation and cytokine expression in murine AIDS-associated interstitial pneumonitis. 903 22


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