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

The transactivating nuclear factor NF-kappa B is believed to be important in the pathophysiology of many cellular systems and mainly during HIV infection. kappa B activation has also been implicated in the process of differentiation as a cell progresses to a more mature and functional stage. As induction of differentiation equals growth retardation we undertook this study in order to establish the role of NF-kappa B in cell growth and maturity. Thus we employed the well described HL-60 cellular system that expresses constitutively basal amounts of NF-kappa B and is susceptible to NF-kappa B induction by various biological or chemical agents. We also used known inducers of differentiation like TNF-alpha, IFN-gamma and IL-4 that interact via their corresponding surface receptors found on HL-60 cells. We first studied by Northern analysis the possible correlation between c-myc and NF-kappa B precursor (p105) mRNA. We witnessed that all three cytokines were able to confer proliferative senescence and down-regulate concomitantly c-myc and NF-kappa B mRNA levels, events chronologically in accord with induction of differentiation as assessed by the induction of HLA-DR surface antigens. It is known that TNF-alpha is capable of inducing nuclear kappa B activity in HL-60 as the cells progress to a more mature stage. Therefore we examined whether the other two cytokines could do the same during the time they lead the cells to a differentiated phenotype. If this was the case, nuclear activation of NF-kappa B should be obtained by the same factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur Cytokine Netw
PMID:One and two-level regulation patterns affecting NF-kappa B mRNA and nuclear NF-kappa B activity after treatment with TNF-alpha, IFN-gamma and IL-4. 849 Jan 2

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)
 ...
PMID:Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. 849 37

High levels of circulating soluble tumor necrosis factor receptors (sTNF-R) are associated with HIV-1 infection and disease. To understand better this association, we have investigated p55 and p75 TNF-R expression on peripheral blood mononuclear cell (PBMC) subsets and in the promonocytic cell line U937, with or without HIV infection. Using flow cytometry and monoclonal antibodies both to sTNF-R and to PBMC subsets, TNF-R were found to be expressed mostly by monocytes and in decreasing amounts and intensity in the following order: CD14+ cells > CD8+ cells > CD4+ cells. Expression of TNF-R was higher on cells obtained from HIV-infected than from noninfected subjects, and expression of p75 sTNF-R was much higher than that of p55 sTNF-R. Studying the U937 cells revealed that over 80% of the cells expressed both sTNF-R, but with greater fluorescence intensity in the HIV-1 chronically infected cells (U-937-IIIB). Treatment of the cells with PMA caused an accelerated release into the medium of both sTNF-R, with a sharp decline in their cell surface expression. Basal levels of mRNA transcripts for p75 TNF-R were higher in the U-937-IIIB cells than in the uninfected cells, but p55 TNF-R mRNA was expressed only in the HIV-1-infected cells. These findings show that HIV-1 infection is accompanied by predominant elevation of p75 TNF-R surface expression on monocytes and CD8+ lymphocytes, and results in both increased message and expression of these receptors in monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
J Interferon Cytokine Res 1995 Sep
PMID:Increased soluble tumor necrosis factor receptor expression and release by human immunodeficiency virus type 1 infection. 853 2

Expression vectors encoding either HIV-1 gp160/rev, gp120, or rev alone were used for direct vaccination of mice and nonhuman primates. Each vaccine elicited long-lived (> 7 months) helper T cell responses in mice and monkeys as measured by in vitro proliferation of splenocytes following recombinant antigen treatment. Cytokine assays of the cell supernatants showed that approximately 100-fold more gamma-interferon than IL-4 was secreted during culture indicating that these vaccines elicited TH1-like responses. CD8+ CTL activities were also observed both in mice and rhesus. The gp120 and gp160/rev vaccines elicited antigen-specific antibodies, although these responses were more variable and lower magnitude for gp160/rev, and gp120 DNA-vaccinated African green monkeys had moderate levels of neutralizing antibodies. No antibodies were found against rev (an intracellular protein) with either rev vaccine. Similar antibody titers were obtained for gp120 by either intramuscular or intradermal injection although T cell responses were generally lower by intradermal route. These results indicate that DNA vaccines may provide a powerful means to elicit cellular and humoral immune responses against HIV.
 ...
PMID:Cytotoxic T lymphocyte and helper T cell responses following HIV polynucleotide vaccination. 854 93

Myeloid cells are important reservoirs of HIV-1 infection. In response to pathogenic agents, macrophages secrete inflammatory cytokines that can modulate viral replication and contribute to AIDS pathogenesis. Because HIV replication is dependent on cellular activation, immunosuppressive cytokines that deactivate macrophages and T cells may be important modulators of an antiviral effect. We tested the anti-HIV potential of the immunosuppressive cytokine-transforming growth factor beta (TGF-beta 1) alone and in combination with AZT in a new monomyeloblastic model of HIV-1 infection. The PLB-985 cell model was infected with HIV IIIB strain, and the course of HIV-1 infection and replication was monitored by reverse transcriptase assay, p24 immunofluorescence, and northern blot analysis of HIV-1-specific mRNA. TGF-beta 1 as a single agent had no effect on the multiplication of HIV-IIIB in de novo-infected PLB 985 monomyeloblastic cells. However, cotreatment with TGF-beta 1 and AZT synergistically slowed virus multiplication within the first week following infection, as determined by reverse transcriptase measurement, p24 antigen detection, and northern blot analysis of viral RNA. The synergistic actions of TGF-beta 1 and AZT were also observed in PLB 985 cells infected with an AZT-resistant strain of HIV-1 (HIV 1393). Synergism between nucleoside analogs and cytokines may be an important therapeutic approach to HIV-1 infection. Elucidation of the role of cytokines in controlling the degree of HIV multiplication may have an impact on both clinical treatments and understanding the progression to AIDS.
J Interferon Cytokine Res 1995 Oct
PMID:Inhibition of human immunodeficiency virus type 1 multiplication by transforming growth factor beta 1 and AZT in HIV-1-infected myeloid cells. 856 6

Proinflammatory cytokines may stimulate replication and spread of HIV. To evaluate to what extent the female genital tract represents a source of these cytokines, we determined TNF-alpha, IL-1 beta and IL-6 concentrations in paired serum and cervicovaginal washings from 45 HIV-negative and 50 HIV-positive women, and then we looked for the relevant mRNAs in cervicovaginal secretions by RT-PCR. Cytokines were detected by ELISA in cervicovaginal fluid from most healthy women. Cervicovaginal washing levels of TNF-alpha were increased above the control value +2 SD in 11/50 HIV-positive women, those of IL-1 beta in 13/50, and those of IL-6 in 14/50. The prevalences of TNF-alpha, IL-1 beta and IL-6 increase and their levels in cervicovaginal washings were significantly higher in the 20 patients at stage IV than in the 30 patients at earlier stages of the disease. In HIV-infected patients, serum and cervicovaginal washing levels correlated positively for TNF-alpha and IL-6, but not for IL-1 beta. Nine of 15 cytokine mRNAs determinations were positive in HIV-infected women versus 1 of 15 in controls (P < 0.01). These findings could be relevant to bidirectional heterosexual transmission of HIV.
Cytokine 1995 Aug
PMID:Proinflammatory cytokine expression in cervicovaginal secretions of normal and HIV-infected women. 858 Mar 74

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.
J Interferon Cytokine Res 1996 Feb
PMID:Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease. 874 65

CD8-depleted PBMCs from 20 HIV-1-seropositive donors were incubated in the presence of no cytokines, rIL-2, rIL-12, or both. HIV-1 replication, measured by culture supernatant p24 Ag, was increased to a comparable extent by either rIL-2 or rIL-12 in five of seven asymptomatic subjects and was not induced by either cytokine in the remaining two asymptomatic subjects. Recombinant IL-2 induced increased p24 in cultures from 8 of 13 symptomatic subjects, but rIL-12 did only in cell lines from 5 symptomatic subjects and then only marginally. In IL-2 containing cultures from subjects with minor symptoms of HIV infection, the mean p24 Ag was 320 +/- 217 pg/ml versus 27 +/- 6 in IL-12-containing cultures (p = 0.03). When rIL-12 was added with rIL-2, p24 Ag levels were reduced fourfold compared to cultures from this group incubated with only rIL-2 (p = 0.03). Neither cytokine had much effect on viral replication in CD8-depleted PBMCs from subjects who had had a major AIDS infection, although the number of CD4 cells in four of six of those cultures was markedly reduced. IL-4, IFN-gamma, and IL-10 production induced by exposure to IL-2 and/or IL-12 were also measured. In CD8-depleted cultures from all infected asymptomatic donors and from some symptomatic donors, addition of rIL-12 to rIL-2 decreased IL-4 and increased both IFN-gamma and IL-10 production. Cytokine-induced production of IL-4, IFN-gamma, and IL-10 was greater in cultures from asymptomatic donors than in cultures from symptomatic subjects. Our results suggest that IL-12 immunotherapy may be complicated by enhancement of viral expression in asymptomatic individuals.
 ...
PMID:Effect of interleukin 12 on in vitro HIV type 1 replication depends on clinical stage. 874 76

Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyzed in HIV+ individuals with different patterns of disease progression to establish correlations between these parameters. Thus, mitogen-stimulated in vitro production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokines) as well as prevalence of viral isolation were evaluated in 26 HIV+ long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressive HIV infection (PI), and in 24 HIV-seronegative controls (HCs). Surface expression of activation and nonactivation markers was also analyzed in a group of these donors. We report that (1) IL-2 and IFN-gamma production is reduced and IL-4 and IL-10 production is increased in PI patients compared to HCs and LTNPs; (2) prevalence of HIV isolation is lower in LTNPs compared to PI, and the primary viral isolates in LTNPs show a slow/low (S/L) phenotype; and (3) the elevated production of type 2 cytokines is paralleled by an increase in CD57+CD4+CD7- lymphocytes. Thus, whereas a high IL-2, high IFN-gamma/low IL-4, low IL-10 cytokine production pattern is present in HC and in LTNP HIV+, progression of HIV infection is associated with a low IL-2 low IFN-gamma/high IL-4, high IL-10 cytokine profile; increased prevalence of HIV isolation; and an augmented percentage of CD57+CD4+CD7- lymphocytes. These findings further confirm that a dominant type 1 cytokine profile together with reduced prevalence of virus isolation is associated with lack of progression in HIV infection.
 ...
PMID:Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection. 882 21

Recombinant interferon-gamma (IFN-gamma) is a potent immune regulatory cytokine and is involved in the defense against several intracellular organisms, such as Chlamydia and Toxoplasma. Furthermore IFN-gamma is able to inhibit the growth of human tumor cell lines. The ability to inhibit the growth of intracellular organisms makes the therapeutic use of recombinant human IFN-gamma in certain patient groups, such as those with chronic granulomatous disease, leprosy, and HIV infection, very attractive. We have shown recently that IFN-gamma-mediated effects can be blocked by heparin and that this inhibitory effect can be abrogated by the addition of protamine. In this report, we show that the antagonistic effect of protamine on heparin-mediated inhibition of IFN-gamma activity is mainly due to the capacity of protamine to enhance IFN-gamma activity. We found that protamine enhances the capacity of IFN-gamma to inhibit the growth of different brain tumor cell lines, to induce indolamine 2, 3-dioxygenase activity, to induce toxoplasmostasis, and to induce MHC class II antigen expression in human glioblastoma cells and in human native fibroblasts. We were able to demonstrate that IFN-gamma binds to protamine, and, therefore, we assume that the effect of protamine on IFN-gamma is due to a direct interaction between the two molecules.
J Interferon Cytokine Res 1996 Jul
PMID:Protamine enhances the activity of human recombinant interferon-gamma. 883 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>