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

Peripheral blood monocytes from human immunodeficiency virus (HIV)-infected individuals or AIDS-related complex/AIDS patients ex vivo exhibit distinct alterations in some but not all immune functions. In studies presented here, monocytes from healthy donors were infected with HIV 1 in vitro and co-cultures with autologous uninfected T lymphocytes were set up. The monocyte/macrophage (M phi)-dependent T cell function was determined by measurement of proliferative and secretory [interleukin (IL)2, interferon-gamma] responses to lectin (phytohemagglutinin), mitogen (anti-CD3 monoclonal antibody), or recall antigen (tetanus toxoid, tuberculin). Accessory function of M phi was normal after HIV infection when optimal amounts (10%-20%) were added to the T lymphocytes. However, HIV infection of M phi significantly decreased T cell proliferative responses and secretion of IL2 when supplemented at limited dilution (0.5%-5%), although interferon-gamma production was not affected. Whereas the lipopolysaccharide-triggered M phi production of IL1 was not impaired by HIV 1 infection, there was a significant decrease in this response when anti-CD3 monoclonal antibody or tetanus toxoid were used to trigger the peripheral blood mononuclear cells. The impairment of proliferation of T lymphocytes in the presence of HIV 1-infected M phi could be overcome by addition of exogenous IL 1. Taken together, these data clearly show that the mononuclear phagocyte-dependent enhancement of stimulated T cell proliferation and lymphokine secretion is decreased when the restricted numbers of monocytes/M phi are HIV 1 infected. There are, therefore, two possible roles of M phi in HIV infection and progression to disease. First, as a reservoir and vehicle for dissemination of the virus, and second, as an immune cell whose essential functions are impaired by infection.
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PMID:Decreased accessory cell function of macrophages after infection with human immunodeficiency virus type 1 in vitro. 225 85

The synthesis of tumor necrosis factor (TNF)/cachectin was assessed in primary monocyte-derived macrophage (MDM) cultures after in vitro infection with a macrophage-tropic strain of HIV-1 (HTLV-IIIBa-L/85). Productive and cytopathic infections in MDM cultures were established using a high multiplicity of infection (m.o.i. = 3) under conditions that minimized endotoxin contamination. Culture supernatants were tested for TNF/cachectin activity by L929 cell cytotoxicity assay, and TNF/cachectin mRNA was assessed by a sensitive PCR amplification technique that could detect between 1 and 10 cells fully activated for TNF/cachectin expression. Unstimulated MDM cultures produced no detectable levels of TNF/cachectin activity or mRNA, consistent with previous demonstrations that production of this cytokine by macrophages is an inducible and not a constitutive event. HIV-1 infection failed to induce detectable TNF/cachectin activity or mRNA in these unstimulated cultures. In addition, the responsiveness of macrophages to lipopolysaccharide (LPS) induction of TNF/cachectin production was assessed in dose-response and kinetic experiments. No differences between infected and uninfected cultures were discernable. These results demonstrate that productive and cytopathic infection with a macrophage-tropic strain of HIV-1 does not alter the regulation of TNF/cachectin expression in macrophages.
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PMID:Human immunodeficiency virus-1 infection of macrophages in vitro neither induces tumor necrosis factor (TNF)/cachectin gene expression nor alters TNF/cachectin induction by lipopolysaccharide. 229 23

Zidovudine (AZT) penetrates human monocytes to exert its antiretroviral activity at the level of reverse transcriptase in infected cells. Stimulation of normal human monocytes with lipopolysaccharide (LPS) results in the transcription of interleukin-1 (IL-1) genes, the intracellular accumulation of IL-1 alpha and IL-1 beta precursors, and the subsequent extracellular release of functional IL-1 beta. The present study demonstrates that zidovudine inhibits the extracellular release of IL-1 activity without affecting the generation of intracellular IL-1 or the amount of released IL-1 beta protein. Similar results were observed with monocytes from normal individuals and monocytes from patients with AIDS. Since IL-1 may upregulate the expression of HIV genes in infected cells, the inhibitory effect of zidovudine on the release of functional IL-1 may be relevant for the beneficial effect of the drug in HIV infection.
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PMID:Zidovudine inhibits functional extracellular monocytic interleukin-1. 235 Apr 46

The production of tumor necrosis factor alpha (TNF alpha) and interleukin 1 (IL-1) was measured in supernatants of cultured peripheral blood monocytes that were obtained from patients with human immunodeficiency virus type 1 (HIV 1) infection and that were purified by counterflow centrifugal elutriation (86-92% purity). TNF alpha levels were significantly higher in monocytes isolated from symptomatic HIV 1-infected patients as compared to normal controls. Although IL-1 levels were also elevated in this group of symptomatic patients they did not reach statistical significance. The production of the two monokines was intermediate in asymptomatic HIV 1-infected individuals. The increase of TNF alpha was observed in the absence of in vitro stimulation as well as in the presence of interferon-gamma plus lipopolysaccharide. TNF alpha and IL-1 were measured by radioimmunoassay and by bioassay, the results of the two methods being highly correlated for both cytokines. The levels of TNF alpha and IL-1 were also positively correlated. These data suggest that IL-1 and TNF alpha may be involved in the pathogenesis of HIV 1 infection.
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PMID:Purified blood monocytes from HIV 1-infected patients produce high levels of TNF alpha and IL-1. 249 10

We measured simultaneously circulating and cell-generated TNF-alpha and IL-1 after lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells (PBMC) by radioimmunoassay (RIA) in HIV-infected individuals at different stages of infection, classified according to CDC classification. TNF-alpha production, both in vitro and endogenous in sera, remained at the normal level in group II patients but was significantly increased in most patients in group IV (P less than 0.05). Most patients of group II and IV displayed normal level of IL-1 in their sera, whereas the level of this monokine generated in vitro was significantly reduced in both groups (P less than 0.05). The cytotoxic effect of factor(s) secreted by PBMC from HIV-infected individuals was evaluated towards a fibroblast cell line L929. The higher titre of cytotoxicity was directly related to a higher production of TNF-alpha by the cells from group IV patients and the effect could be removed by pre-absorption with anti-TNF-alpha monoclonal antibody.
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PMID:Production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in patients with AIDS. Enhanced level of TNF-alpha is related to a higher cytotoxic activity. 261 49

In an attempt to assess the role of immune cytotoxic activity in the sequence of events leading to the acquired immunodeficiency syndrome (AIDS), natural cytotoxic activity was studied in 17 asymptomatic homosexual males, seropositive for anti-human immunodeficiency virus (HIV) antibodies, as compared to 16 of their seronegative counterparts and to 14 control healthy heterosexual individuals. Cell (contact)-mediated cytotoxicity (CMC) as well as cytotoxin (CTX) production by lipopolysaccharide (LPS)-stimulated, phytohemagglutinin (PHA)-stimulated, HeLa tumor cell-stimulated, and unstimulated peripheral blood mononuclear cells (PBMC) were determined using HeLa cell monolayer cultures, sensitized with cycloheximide, as targets. The CMC was markedly enhanced in the seropositive group (28 +/- 21 (mean +/- SD) lytic units/10(6) PBMC) as compared to the seronegative group (17 +/- 7; P less than 0.005) and to the heterosexual group (13 +/- 6; P less than 0.05). Likewise, CTX production by unstimulated PBMC from seropositive homosexuals (19 +/- 26 units/ml) was higher than that observed in the other groups (both 4 +/- 4 units/ml; P less than 0.05). CTX production by PHA-stimulated, LPS-stimulated, and HeLa cell-stimulated PBMC was significantly enhanced in both the seropositive and seronegative groups in comparison to the normal heterosexual controls. These results suggest that increased cytotoxic activity may be present in homosexuals prior to their exposure to HIV, and may be further enhanced after HIV infection.
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PMID:Possible role of natural cytotoxic activity in the pathogenesis of AIDS. 278 1

We have infected peripheral blood-derived monocyte/macrophage cultures with HIV-1 in order to determine the effect of such infection on cellular immunoregulatory function. We have confirmed that monocytes/macrophages are susceptible to infection by HIV-1, as determined by in situ hybridization using a HIV-1-specific RNA probe and by the presence of reverse transcriptase activity in culture supernatants. The cells employed efficiently supported viral replication in the absence of significant cytopathic effect, and secreted as little as 20% of the amount of IL-1 activity of uninfected controls in response to stimulation with either latex beads or lipopolysaccharide. This effect was not observed when UV-inactivated HIV-1 was used to infect the cells.
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PMID:Infection of human monocytes/macrophages by HIV-1: effect on secretion of IL-1 activity. 326 May 78

To investigate differences among brain-derived microglia and other classes of immune cells, we compared the morphologies and growth properties of mononuclear phagocytes isolated from tissues of the newborn rat. Scanning EM shows that microglia from postnatal rat brain are covered with spines (typically > 20 per cell body) in a distinctive manner which contrasts the smooth surfaces of bone marrow cells and the ruffled surfaces of tissue macrophages from spleen, liver, and peritoneum. The spine-bearing surface of microglia is a specific cell marker, for it does not change with age or after exposure to cytokines or other immunostimulants. Approximately 99% of mononuclear phagocytes cultured from normal adult rat brain are spinous microglia. Five days after injury to rat brain, cells at sites of Wallerian degeneration are essentially all spinous ones while nearly 30% of cells found within areas of infarction or penetrating trauma are invading macrophages. In a similar way, nearly all cells isolated from normal, postmortem adult human brain are spine-bearing microglia (> 99% homogeneity). Brains from patients with amyotrophic lateral sclerosis contain only spinous microglia whereas cells from HIV-1 infected brains include significant numbers of invading ruffled macrophages. Cultured microglia, unlike cultured bone marrow precursors, monocytes, or tissue macrophages, spontaneously develop long, thin processes that extend hundreds of microns in length. Microglia retract these processes after exposure to fetal bovine serum, laminin, or such immunostimulants as recombinant murine interferon gamma (rmIFN gamma) and lipopolysaccharide. Of all types of mononuclear phagocytes tested, only microglia differentiate into quiescent ramified cells when in contact with astrocytes. Thus, microglia represent a unique class of cell maintained, in part, by astroglia as dormant, ramified mononuclear phagocytes in mature CNS. Application of cell surface criteria described here will allow study of distinct populations of mononuclear phagocytes associated with neurologic disorders.
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PMID:Cell surface morphology identifies microglia as a distinct class of mononuclear phagocyte. 747 22

Chronic ethanol (EtOH) abuse in humans leads to a variety of immunomodulatory events that can alter resistance to a number of infectious agents. Whether alcohol abuse affects the susceptibility to human immunodeficiency virus infection or the subsequent development of acquired immune deficiency syndrome (AIDS) is a matter of extreme importance; however, available information in humans or animal models is limited. The goal of this study was to evaluate the effect of chronic EtOH feeding in mice on the development of immunodeficiency in the murine model of AIDS (MAIDS). C57BI/6 mice were placed on the Lieber-DeCarli liquid EtOH diet (25% or 31% total caloric intake) or a nutrient-matched isocaloric liquid control diet. Seven days later, mice were infected with the LP-BM5 murine leukemia virus mixture, and groups of infected and noninfected mice were assayed at defined time points postinfection for antigen-specific and nonspecific immune responses. In the absence of retroviral infection, chronic EtOH feeding (5-8 weeks) led to reductions in spleen weights, compared with isocaloric controls. In spite of reduced spleen size, mitogenic responses of spleen cells to concanavalin A (ConA) and lipopolysaccharide (LPS) were elevated in EtOH-fed mice, as compared with mice fed the control diet. Chronic EtOH feeding also enhanced the allogeneic mixed lymphocyte response and increased antigen-specific priming of both B-cells and CD4+ T-cells to the antigen, sheep red blood cells. In MAIDS-infected mice, chronic EtOH feeding delayed but did not prevent the onset of virus-induced immunodeficiency and MAIDS-induced autoantibody synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol as a possible cofactor in the development of murine AIDS. 748 39

Since early growth response-1 (Egr-1) is required for macrophage differentiation and nitric oxide (NO) is immunosuppressive, we hypothesized that NO would reduce Egr-1 expression in rat lung macrophages. The inflammatory stimuli interferon-gamma and lipopolysaccharide induced an early, transient increase in Egr-1 mRNA (> 5-fold at 2 h) and a sustained, high level of inducible NO synthase mRNA (> 100-fold from 4 to 24 h). The NO metabolites nitrite and nitrate rose > 10-fold in medium from stimulated versus unstimulated cells over 24 h. Concomitant with elevated nitrogen oxides, Egr-1 mRNA levels declined to 80% below unstimulated cells at 24 h. This decline was blocked by an inhibitor of NO production, NG-monomethyl-L-arginine. Further, the NO donor S-nitroso-N-acetylpenicillamine inhibited Egr-1 expression in a dose-dependent manner, producing complete inhibition at 0.5 mM. The effect of S-nitroso-N-acetylpenicillamine was not due to reduced macrophage viability. We conclude that Egr-1 induction precedes inducible NO synthase induction in stimulated rat macrophages and that subsequent NO production reduces macrophage expression of Egr-1. We propose that this mechanism is used to regulate macrophage differentiation in human immunodeficiency virus infection and other inflammatory states.
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PMID:Nitric oxide reduces early growth response-1 gene expression in rat lung macrophages treated with interferon-gamma and lipopolysaccharide. 752 82


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