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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Cytokines are a group of secreted proteins that display diverse biological activity. They are especially important in the body's response to injury. They subserve a variety of both autocrine and paracrine functions by activating numerous intracellular second-messenger signaling pathways. Cytokines are known to mediate many inflammatory processes, and the inappropriate presence of cytokines in the central nervous system (CNS) has been implicated in a number of disease states. This article focuses on the biological role of two cytokines, namely: tumor necrosis factor alpha (TNF-alpha), and interferon-gamma (IFN-gamma), in the progression of neurologic disorders such as multiple sclerosis (MS) and AIDS dementia complex (ADC), with an emphasis on cytokine effects on glial cells. We discuss the cellular source of each cytokine within the CNS, their receptors, and what signaling pathways are involved in mediating their actions. We also describe recent findings indicating that HIV viral proteins, i.e., gp120, can activate cells of the CNS in a comparable manner as cytokines, and discuss the second messengers that mediate gp120-induced responses. We conclude by identifying potentially important areas of cytokine research in the context of neurologic disease.
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PMID:TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function. 852 37

We have previously shown that the treatment of monocytes with interferon-gamma (IFN-gamma) prior to exposure with human immunodeficiency virus type-1 (HIV) results in complete inhibition of HIV infection of monocytes. In the present report, we have extended this study to obtain information on the mechanism(s) underlying IFN-gamma-induced inhibition of HIV infection of monocytes. To examine the effect of IFN-gamma on HIV entry, the first event in the infectious cycle of the virus, we amplified HIV-gag sequences in the genomic DNA and RNA of IFN-gamma treated monocytes, and found no evidence for the presence of either proviral DNA or HIV RNA sequences. These results were consistent with the absence of intracellular HIV particles either in the latent or actively replicating state as determined by flow-cytometric analysis of these cells. Furthermore, no HIV-induced cytopathic effects, such as multinucleated giant cell formation or cell death, were observed in IFN-gamma-treated monocytes after their exposure to HIV. Stimulation of IFN-gamma-treated monocytes 6 days postinfection with tumor necrosis factor-alpha (TNF-alpha), which is known to augment HIV replication in the infected cells, did not result in the induction of the HIV indicating the absence of latent HIV infection in IFN-gamma-treated monocytes. Treatment of monocytes with IFN-gamma, TNF-alpha, or with a combination of the two agents which is known to induce antimicrobial free radical nitric oxide (NO2- in the murine system did not induce NO2- production human monocytes suggesting the antiviral activity of IFN-gamma to be independent of NO2(-)-mediated killing of HIV or HIV-infected monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-gamma-induced downregulation of CD4 inhibits the entry of human immunodeficiency virus type-1 in primary monocytes. 855 5

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

Expansion of a CD57+CD8+ T lymphocyte subset has been reported in HIV and human cytomegalovirus (HCMV) infection. Almost all of these T cells lack CD28 expression. While CD28- cells are often associated with anergy, some authors believe their expansion in HIV infection precipitates immunodeficiency. We studied 15 randomly chosen patients with immune activation and observed that CD57+CD28- T cell expansion may occur in various conditions and to the same degree as in HIV infection without resulting in immunodeficiency. Triple colour flow cytometry also revealed that the CD57 and CD28 antigens are coexpressed in only 3% of CD8+ T cells, irrespective of the underlying condition, so that almost all CD57+CD8+ cells are always CD28-. Analysis of Fas (CD95) expression with respect to CD28 expression on CD4+ and CD8+ T cells from 10 additional patients indicated no increased commitment to apoptosis in CD28- T cells. Semiquantitative polymerase chain reaction (PCR) comparing CD28+ and CD28-CD8+ T cells with respect to cytokine gene expression (tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1beta) in five renal transplant patients with expansion of the CD57+ subset detected no cytokine gene expression deficit in CD28- T cells. A direct association of increased proportions of CD57+CD28-CD8+ T cells with immunodeficiency/anergy is disputed.
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PMID:The enigma of CD57+CD28- T cell expansion--anergy or activation? 860 25

Human gamma delta T lymphocytes expressing the variable T cell receptor elements V gamma 9 paired with V delta 2 are activated by antigen derived from Mycobacterium tuberculosis (M. tb.) and presented by antigen-presenting cells (APC). The subsequent proliferation is strictly dependent on the presence of CD4+ TCR alpha beta+ T helper type 1 (Th1) cells producing interleukin-2 (IL-2). In this study, we report that the reactivity of V gamma 9 cells to M. tb. stimulation in vitro was drastically decreased or absent in the majority of the analyzed HIV-1-infected individuals (CDC stages III and IV). We show that the failure of V gamma 9 cells from HIV+ individuals to proliferate following M. tb. stimulation was not due to an intrinsic qualitative or quantitative defect of gamma delta T cells but rather to a deficiency of M. tb.-reactive CD4 Th1 cells. Thus, V gamma 9 responsiveness could be restored if cultures of M. tb.-stimulated T cells from HIV+ donors were reconstituted with one of the following: (i) exogenous IL-2 (ii) purified CD4 T cells from allogeneic donors; or (iii) T cell-depleted APC from allogeneic donors. In the majority of HIV+ patients, the defective Th1 activity of M. tb.-stimulated CD4 T cells could be decreased neither by cytokines known to favor Th1 development (IL-12, interferon-gamma) nor by neutralization of the Th1-suppressing Th2 cytokine IL-10. We suggest that measurement of V gamma 9 cell expansion within M. tb.-stimulated peripheral blood mononuclear cells provides a sensitive assay for the functional capacity of antigen (M. tb.)-specific CD4 Th1 cells in HIV-infected individuals.
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PMID:Mycobacteria-reactive gamma delta T cells in HIV-infected individuals: lack of V gamma 9 cell responsiveness is due to deficiency of antigen-specific CD4 T helper type 1 cells. 860 21

The CD40 antigen is a member of the tumor necrosis factor receptor/nerve growth factor receptor superfamily and is involved in cell proliferation, differentiation, and survival. Using different monoclonal antibodies, we found CD40 expression by immunohistochemistry on CD31- and CD34-positive Kaposi's sarcoma spindle cells in all tumors of 18 HIV-1 seropositive and 4 HIV-1 seronegative patients. Western blot analysis of tumor lysates detected a 48- to 50-kd glycoprotein corresponding to the CD40 antigen expressed by B lymphocytes. CD40 expression was also detectable in one of four cultures of spindle cells derived from Kaposi sarcoma tissue. Treatment of the CD40-positive spindle cells but not of the CD40-negative ones with interferon-gamma up-regulated CD40 surface expression. Besides on Kaposi sarcoma tumor cells, CD40 was distinctly present on vascular endothelial cells in areas within and adjacent to the tumors and in benign inflammatory lesions such as granulation tissue of HIV-1-negative patients. In contrast, CD34-negative endothelia of thin walled vessels, most likely lymphatics, were predominantly CD40 negative. Only faint or no CD40 expression was found on endothelial cells in normal skin. We conclude from our data that expression of the CD40 antigen by endothelial cells is up-regulated during tissue inflammation. As signaling through CD40 is able to increase cell survival, expression of CD40 by Kaposi sarcoma tumor cells might play an important role in the pathogenesis of this neoplasm.
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PMID:CD40 antigen is expressed by endothelial cells and tumor cells in Kaposi's sarcoma. 862 2

Evidence is accumulating that T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals show accelerated cell death through apoptosis. We have recently demonstrated that the cross-linking of CD4 molecules (CD4XL) results in death of normal peripheral T cells through apoptosis and imbalanced cytokine secretion (ie, induction of tumor necrosis factor-alpha [TNF-alpha] and interferon-gamma [IFN-gamma] in the absence of interleukin-2 [IL-2] or IL-4 secretion). These upregulated cytokines (TNF-alpha/IFN-gamma) largely contributed to upregulation of the apoptosis-inducing cell surface molecule, Fas (APO-1/CD95) and apoptosis induction. The present study investigated the effect of vesnarinone as a novel immunomodulating agent on CD4XL-induced T-cell apoptosis. The addition of vesnarinone to peripheral blood mononuclear cells (PBMC) significantly inhibited CD4XL-induced lymphocyte apoptosis. This apoptosis-inhibitory effect of vesnarinone was associated with the blocking of CD4XL-induced TNF-alpha IFN-gamma secretion and of Fas antigen upregulation. However, vesnarinone did not block effects of exogenously supplemented TNF-alpha/IFN-gamma on Fas induction. These data suggest that vesnarinone inhibits CD4XL-induced TNF-alpha/IFN-gamma secretion, thereby blocking subsequent Fas upregulation and apoptosis induction. Given the potent pathogenic role of imbalanced cytokine secretion observed in HIV-infection, an agent such as vesnarinone may be of therapeutic value in slowing disease progression.
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PMID:Inhibition of CD4 cross-linking-induced lymphocytes apoptosis by vesnarinone as a novel immunomodulating agent: vesnarinone inhibits Fas expression and apoptosis by blocking cytokine secretion. 863 Mar 99

At an outpatient AIDS research clinic in Kinshasa, Zaire, physicians conducted a medical examination and took blood samples from 48 women with AIDS, 51 women with asymptomatic HIV-1 infection, and 11 healthy HIV-1 seronegative women to study the relationship of circulating cytokines and cytokine antagonists to the progression of HIV-1 infection. Asymptomatic HIV-1-infected women had higher levels of the cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) than AIDS cases and controls (320 vs. 156 pg/ml, p 0.001, and 210 vs. 78 pg/ml, p 0.001, respectively) and even higher levels of interleukin-1Ra and TNFsRp55 (both natural cytokine antagonists) (4300 vs. 100 pg/ml, p 0.001; and 12,500 vs. 1450 for the AIDS group [p 0.0001] and 950 for controls [p 0.001]). The high levels of the two proinflammatory cytokines in asymptomatic HIV-1 infected women suggests that the high levels of antagonist cytokines blocked the clinical effects of interleukin-1beta and TNF-alpha. 46 AIDS patients had no detectable interleukin-1beta. 42 AIDS patients had no detectable TNF-alpha. The lack of cytokines in most AIDS patients suggests that persons in end-stage HIV-1 disease have a limited capacity to synthesize cytokines, perhaps depleting the remaining cytokine-producing central and peripheral lymphoid tissues. Asymptomatic HIV-1-infected women also had higher levels of interleukin-8 than AIDS cases and controls (750 vs. 40 pg/ml; p 0.001). 11 of the 13 highest values of interferon-gamma (11 pg/ml) belonged to AIDS patients rather than asymptomatic HIV-1-infected cases (p = 0.005). In the last 2 months, AIDS patients with detectable interferon-gamma had fever of longer duration than those with no interferon-gamma (17 vs. 9 days, p = 0.05), indicating that AIDS cases with interferon-gamma were still capable of responding to inflammatory stimuli. These findings suggest that cytokine antagonists may modulate cytokine-associated symptoms in the early phases of HIV-1 infection.
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PMID:Plasma cytokines, cytokine antagonists, and disease progression in African women infected with HIV-1. 863 37

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8+ lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8+ cells in a group of LTNP patients who had stable CD4+ cell counts (> 500/mm3) for at least 7 years. Their CD8+ absolute numbers were similar to a control group composed of HIV-1+ patients who have a progressive decline of their CD4+ cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28+, CD95 strongly positive CD8+ population, while disease progression is marked by the CD28-CD95+CD8+ subset. Purified CD8+ cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-gamma) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8+ cells from progressors are unable to secrete IL-2 and IL-10. Although CD8+ cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8+ T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8+ cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.
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PMID:CD8+ lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection. 870 25


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