Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The infectious disease background and particularly the helminth infections that are endemic in Africa could have profound effects on the host immune system. Studies that we have performed on an Ethiopian HIV- immigrant population that has recently reached Israel, lend support to this notion. They have indeed revealed a very high prevalence of helminth and several other infections with an extreme immune dysregulation, consisting of: (i) highly elevated plasma IgE, IgG, placental isoferritin, p75 soluble TNF receptor (sTNFR) levels and very high blood eosinophilia; (ii) increased secretion from phytohaemagglutinin (PHA)-simulated peripheral blood mononuclear cells (PBMC) of the cytokines IL-2, IL-4, IL-10 and p75 sTNFR, and decreased secretion of interferon-gamma (IFN-gamma) and IL-6; (iii) increased and decreased surface expression of p75 TNFR and IL-6 receptor on lymphocytes, respectively. The causal relationship between this immune dysregulation and the infectious background is highly suggestive, and could have far-reaching implications in the resistance to other infections.
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PMID:Immune dysregulation in Ethiopian immigrants in Israel: relevance to helminth infections? 856 6

Previous studies of asymptomatic human immunodeficiency virus (HIV) infection have shown that serum levels of soluble tumor necrosis factor receptors (sTNFR) are good predictors of disease progression and clinical outcome during zidovudine (ZDV) therapy. The present study of symptomatic HIV infection was designed to evaluate whether sTNFR p55 and p75 at weeks 0 (pretreatment) and 24 and 48 are predictors of death < or = 3 years after the start of ZDV 1,000 mg alone or combined with low-dose interferon-alpha (ZDV 500 mg + IFN-alpha 3 MIU three times weekly). CD4+ T-cell numbers and serum neopterin were analyzed in a similar way. Forty previously untreated symptomatic HIV-infected persons with CD4+ T-cell numbers > or = 150 x 10(6)/L were included. At baseline, in the nonsurvivor group, mean age (42.1 vs. 34.4 years, p = 0.002) and neopterin (24.7 vs. 18.0 nmol/L, p = 0.02) were higher, whereas mean CD4+ T-cell counts (202 vs. 295 x 10(6)/L, p = 0.02) were lower than in the survivors. All analyses were adjusted for age. For the pretreatment marker values, a significant relative risk (RR) for death was noted only in the univariate analysis for sTNFR-p55 > 1.7 ng/ml [RR 3.1; 95% confidence interval (CI) 1.1-8.8; p = 0.04]. During therapy, CD4+ counts < 200 x 10(6)/L at week 24 and 48 and neopterin > 20 nmol/ml at week 48 were independent predictors of survival in the uni- and multivariate analysis. Marker values relative to baseline were not predictive. sTNFR-p55 and p75 were of little use as surrogate markers for clinical efficacy during ZDV-containing drug regimens in symptomatic HIV-infected patients with CD4+ counts 150 x 10(6)/L.
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PMID:Predictive value for survival of soluble tumor necrosis factor receptors p55 and p75 during zidovudine-containing treatment in symptomatic human immunodeficiency virus type 1 infection. 875 25

Tumor necrosis factor alpha (TNF-alpha) is a potent inducer of human immunodeficiency virus type 1 (HIV-1) expression in chronically infected cells. The aim of this study was to investigate the role played by the two known TNF-alpha receptors, TNFR-p55 and TNFR-p75, in the activation of HIV-1 expression. As a model system the latently infected human promonocytic cell line U1 was stimulated with wild-type TNF-alpha, with TNF-alpha muteins that specifically bind to one or the other receptor or with receptor-specific monoclonal antibodies. Induction of HIV-1 expression, measured by p24 core antigen capture enzyme-linked immunosorbent assay (ELISA), was found to be exclusively triggered by TNFR-p55 stimulation. However, our results also showed that the addition of TNFR-p75-specific ligands negatively modulated the HIV-1 expression induced via TNFR-p55.
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PMID:Tumor necrosis factor receptor p55 mediates induction of HIV type 1 expression in chronically infected U1 cells. 883 97

Two different receptors exist for tumor necrosis factor-alpha (TNF-alpha), designated as p55 (TNF-RI) and p75 (TNF-RII). Soluble (= s) forms of TNF-Rs are secreted after proteolytic cleavage and block the effects of TNF-alpha. sTNF-RI, sTNF-RII and the soluble interleukin 2 receptor (sIL-2R) were determined by ELISA in serum samples of HIV-infected children and adolescents. Twelve children with vertical HIV infection (mean age +/- SD, 5.9 +/- 3.8 years) and 17 horizontally infected patients (16.1 +/- 7.3 years) were classified according to the revised CDC criteria. Twenty healthy control persons (6.4 +/- 5.8 years) showed the following receptor concentrations (median): sTNF-RI 888 pg/ml, sTNF-RII 1,741 pg/ml, sIL-2R 94 pM. Compared to controls, horizontally HIV-infected patients had significantly (Mann-Whitney U test) higher levels for sTNF-RI (median 1,192 pg/ml), sTNF-RII (3,481 pg/ml) and sIL-2R (128 pM). For vertically infected children only sTNF-RII (2,944 pg/ml) was significantly elevated compared to controls. There were no differences in soluble receptor levels between vertical or horizontal transmission. Surprisingly, no significant differences for sTNF-RI, sTNF-RII and sIL-2R occurred when 19 patients in stage CDC I were compared to ten patients in stages II or III. The clearly elevated sTNF-RII levels in patients with horizontal and vertical HIV infection indicate the activation of the monocyte/macrophage system in both groups.
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PMID:Increased serum levels of soluble tumor necrosis factor receptors (sTNF-Rs) in children and adolescents with vertically and horizontally transmitted HIV infection. 887 82

We determined the degree of activation of the TNF alpha system and the levels of IL-8 in HIV-1 infection. TNF alpha is one of the most potent agents for the induction of IL-8. TNF alpha may be cleared rapidly from the circulation, however soluble tumor necrosis factor receptor (sTNFR) p75 which is more stable may reflect the degree of activation of the TNF alpha system. We measured concentrations of sTNFR p75 and IL-8 with immunoassays in the plasma of 99 HIV-1-infected patients at different stages of disease (Centers for Disease Control classification) and in 20 healthy control subjects. Plasma levels of sTNFR p75 were elevated in most of the asymptomatic seropositive patients without CD4+ T cell depletion (Stage IIA) and in most of patients of all clinical groups compared with controls. However, in the majority of those patients plasma levels of IL-8 were not higher than those of controls. Our results suggest that sTNFR p75 levels but not IL-8 levels in circulating blood are high in the course of HIV-1 infection.
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PMID:Plasma levels of sTNFR p75 and IL-8 in patients with HIV-1 infection. 887 20

T cell apoptosis has been proposed as an important contributor to the functional defects and depletion of T cells in HIV-infected individuals. However, the mechanisms involved in this apoptosis have not been elucidated. We recently showed that peripheral blood T cells from HIV-infected individuals are especially susceptible to Fas antigen-induced apoptosis. In this study we examine the role of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR) and CD30, receptors known to be involved in T cell activation-induced cell death (AICD), in the spontaneous and activation (anti-CD3)-induced apoptosis of peripheral blood T cells from asymptomatic HIV-infected individuals. We report here that spontaneous and activation-induced T cell apoptosis cannot be inhibited by reagents that block interactions of Fas, CTLA-4, p55 and p75 TNFR and CD30 with their respective ligands. We also show that IL-12, IFN-gamma, IL-4 and IL-10 cannot modify spontaneous, activation- and anti-Fas-induced apoptosis. Anti-Fas preferentially induced CD4+ T cell apoptosis whereas AICD induced apoptosis equally in CD4+ and CD8+ T cells. We conclude that T cell AICD in HIV infection is not mediated by Fas, thus indicating that Fas-induced and activation-induced T cell apoptosis are independent mechanisms of apoptosis which may play different roles in the pathogenesis of HIV infection.
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PMID:Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals. 891

Recently, a HIV-dependent upmodulation of the p75 tumour necrosis factor receptor (TNFr75) was observed using latently-infected OM-10.1 promyelocytes; although the participation of TNFr75 in HIV-1 activation remained undefined. Here, using receptor cross-linking by agonistic antibodies, no direct HIV-1 activation via TNFr75 was observed. Signalling via the p55 tumour necrosis factor receptor (TNFr55) accounted for the full extent of HIV-1 activation in OM-10.1 cultures. However, in tumour necrosis factor alpha (TNF-alpha) dose titration experiments, antibody blockade of TNFr75 decreased the dose response markedly, indicating a ligand passing function. TNFr75 blockade did not alter the dose response to agonistic TNFr55 antibody induction; verifying that the effect on the TNF-alpha dose response was not due to negative signalling or cytolysis. These results demonstrate that, although not directly involved in signal transduction resulting in HIV-1 activation, TNFr75 can serve a critical ligand passing function and permit continued HIV-1 expression during limited TNF-alpha availability.
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PMID:Ligand passing by the p75 tumour necrosis factor receptor enhances HIV-1 activation. 898 Aug 75

Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines that play a central role in regulating HIV-1 replication. These cytokines express their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75-80). In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production. Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood lymphocytes cocultured with cells expressing membrane TNF underwent rapid induction of apoptosis with a subsequent reduced HIV production of these lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated with soluble TNF. These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.
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PMID:Membrane tumor necrosis factor (TNF) induced cooperative signaling of TNFR60 and TNFR80 favors induction of cell death rather than virus production in HIV-infected T cells. 899 44

The proinflammatory cytokine IL-1beta is thought to be involved in ongoing HIV disease. Furthermore, its naturally occurring inhibitors soluble IL-1 receptor type II (sIL-1RII) and IL-1 receptor antagonist (IL-1Ra) may play a pivotal role in regulating its biological action. To investigate the involvement of the IL-1 system we determined serum levels of IL-1beta, IL-1Ra and sIL-1RII in 90 HIV- patients. The obtained values were compared with markers of disease progression such as CD4+ count, 5'-neopterin. Beta2-microglobulin and soluble tumour necrosis factor receptors (sTNF-R) p55 and p75 and then compared with C-reactive protein (CRP), granulocyte count, IL-6 and TNF-alpha. While IL-1Ra concentrations increased significantly with progressive CDC disease stages, sIL-1RII and IL-1beta were not altered in our cohort. IL-1Ra showed statistical relation to decreasing CD4+ lymphocytes and increasing 5'-neopterin, beta2-microglobulin, sTNF-R p55, sTNF-R p75. Furthermore, IL-1Ra correlated positively with serum IL-6, TNF-alpha, CRP and granulocytes. In contrast, sIL-1RII and IL-1beta tended to show an inverse correlation or showed no significant relationship to all these parameters. IL-1beta was measurable only in a limited number of samples. IL-1Ra showed a clear relationship to acute inflammatory events as well as to the different disease stages. Our data suggest a dissociation between IL-1Ra and sIL-1RII serum levels which may indicate that the two IL-1 binding proteins have different pathophysiological roles in HIV infection.
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PMID:The IL-1 system in HIV infection: peripheral concentrations of IL-1beta, IL-1 receptor antagonist and soluble IL-1 receptor type II. 921 24

The correlation of persistent tumor necrosis factor-alpha (TNF-alpha) activation with disease progression in patients infected with human immunodeficiency virus type 1 (HIV-1), suggests a role for TNF-alpha in the pathogenesis of HIV-1 infection. In the present study, we examined by flow cytometry the expression of membrane-bound (m) components of the TNF system in 33 HIV-1-infected patients and 12 healthy controls. While peripheral blood mononuclear cells (PBMC) from asymptomatic and symptomatic non-acquired immune deficiency syndrome (AIDS) patients showed a significantly increased percentage of mTNF-alpha+ and mTNF receptor (TNFR)+ cells compared with controls, this was not found in the AIDS group. Compared with healthy controls, AIDS patients had a significantly decreased percentage of both monocytes and lymphocytes expressing p75-TNFR. PBMC from AIDS patients showed a higher p75-TNFR mRNA level and a higher spontaneous release of soluble p75-TNFR than healthy individuals, suggesting enhanced cell surface turnover of this TNFR. The low expression of TNFRs on both lymphocytes and monocytes in the AIDS group was associated with high numbers of HIV-1 RNA copies in plasma, low numbers of CD4+ lymphocytes, and high serum levels of soluble TNFRs. AIDS patients had a decreased percentage of CD8+ lymphocytes expressing TNFRs compared with healthy controls. In contrast, these patients, as well as symptomatic non-AIDS patients, had an increased percentage of TNF-alpha+ and TNFRs+ cells among remaining CD4+ lymphocytes. The pattern of abnormalities seen in AIDS patients suggests a role for persistent activation of the TNF system in the accelerated CD4+ lymphocyte destruction, the enhanced HIV-1 replication, and the markedly impaired antimicrobial defense in advanced HIV-1-related disease.
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PMID:Dysregulation of membrane-bound tumor necrosis factor-alpha and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection: low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load. 932 34


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