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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages, unlike CD4+ T cells, can be productively infected by human immunodeficiency virus (HIV) without prior cellular activation. Cytopathic infection ensues without the induction of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), or tissue factor genes. In detailed studies on TNF alpha, HIV infection did not affect the regulation of TNF alpha in response to bacterial lipopolysaccharide. In an effort to examine the interferon responsiveness of HIV-infected macrophages, the cells were challenged with vesicular stomatitis virus (VSV) with or without interferon pretreatment. Surprisingly, HIV-infected macrophages were completely resistant to VSV-induced lysis even in the absence of interferon; however, no interferon was detected in the supernatants of these infected cells. The resistance of HIV-infected macrophages to superinfection with VSV indicates a previously undescribed effect of HIV upon macrophage cellular metabolism.
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PMID:Characterization of a macrophage-tropic HIV strain that does not alter macrophage cytokine production yet protects macrophages from superinfection by vesicular stomatitis virus. 217 98

The study of monocyte/macrophage functions after human immunodeficiency virus type 1 (HIV-1) infection may help in understanding the pathogenesis of AIDS. The production of four cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF), by peripheral blood monocytes/macrophages was evaluated after in vitro infection with HIV-1. HIV-1 infection of these monocytes/macrophages did not result in release of any of these cytokines. Similarly, treatment of uninfected cells with purified recombinant HIV-1 envelope protein did not result in cytokine production. After stimulation with endotoxin or endotoxin plus interferon-gamma, HIV-1-infected monocytes/macrophages produced amounts of TNF alpha, IL-6, GM-CSF, and IL-1 beta comparable to that of uninfected cells. HIV-1 infection does not appear to induce or alter cytokine production by mononuclear phagocytes, which retain the capacity to produce these cytokines after endotoxin stimulation.
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PMID:Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1). 218 29

A promonocytic cell model was used to investigate cytokine gene transcription in U937 and U9-IIIB cells chronically infected with human immunodeficiency virus type 1 (HIV-1). The production of interferon (alpha-1 interferon [IFN-alpha 1], IFN-alpha 2, and IFN-beta), interleukin (interleukin 1 alpha [IL-1 alpha], IL-1 beta, and IL-6), and tumor necrosis factor alpha (TNF-alpha) mRNA was characterized by quantitative polymerase chain reaction mRNA phenotyping in U937 and U9-IIIB cells following coinfection with Sendai paramyxovirus or stimulation with lipopolysaccharide (LPS). Chronic HIV-1 infection of U9-IIIB cells resulted in a low constitutive level of transcription of TNF and IL-1 genes but not IFN genes; however, when the cells were coinfected with Sendai virus, 10- to 20-fold higher levels of IFN-beta, IL-1 beta, IL-6, and TNF-alpha mRNA were observed in U9-IIIB cells than in similarly induced U937 cells. The enhanced levels of cytokine RNA in virus-infected U9-IIIB cells were also accompanied by higher levels of IFN antiviral activity and TNF secretion than in U937 cells. Transcript levels for IFN-alpha 1 and IFN-alpha 2 were equivalently induced in virus-infected U937 and U9-IIIB cells, indicating that a generalized derepression of cytokine gene expression did not occur as a consequence of HIV-1 infection. When LPS was used as an inducer, a distinct pattern of cytokine gene expression was detected in U9-IIIB cells. TNF-alpha and IL-1 beta but not IFN-alpha or IFN-beta transcripts were induced by LPS. These results suggest that HIV-1 infection of promonocytic cells may prime or sensitize cells such that subsequent antigenic challenge leads to coordinate enhancement of cytokine gene expression.
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PMID:Coordinate enhancement of cytokine gene expression in human immunodeficiency virus type 1-infected promonocytic cells. 224 88

Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN-beta were not detected nor was the mRNA expressed in either uninfected or HIV-infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV-infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes was coincident with high levels of 2',5' oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells. The markedly diminished capacity of HIV-infected monocytes to produce IFN-alpha may reflect a specific adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.
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PMID:A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. 198 24

Expression of tumor necrosis factor (TNF alpha), tissue factor (TF), and interleukin 1-beta (IL-1 beta) mRNA was evaluated in monocytes isolated from patients infected with human immunodeficiency virus (HIV). There was a significant depression (66%) of the induced level of TF mRNA expression in response to lipopolysaccharide. Conversely, the response of TNF alpha and IL-1 beta, following LPS induction, was "normal." TF mRNA reduction was also observed to a lesser degree in AIDS-related complex patients (20%) but not in asymptomatic seropositives. TF is necessary for initiation of the coagulation protease cascade, leading to thrombin production and fibrin deposition, which play a role in inflammatory responses. Its selective reduction may be a factor in the diminished resistance to secondary infections observed in AIDS. Further, since the TF defect increases as patients progress toward AIDS, it may serve as a marker for disease progression.
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PMID:A selective defect in tissue factor mRNA expression in monocytes from AIDS patients. 229 2

The production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) by fresh peripheral blood mononuclear cells was evaluated after exposure to human immunodeficiency virus (HIV) or purified recombinant HIV-1 envelope glycoprotein (rgp120). To exclude the role of contaminating endotoxin in this study, all media were subjected to ultrafiltration and reagents contained less than 25 pg of endotoxin per ml by Limulus assay. Under endotoxin-free conditions, no increases in IL-1 beta, IL-6, or TNF-alpha mRNA or protein were detectable in cell cultures exposed to HIV-1, HIV-2, or rgp120 (0.1 to 10 micrograms/ml), as compared with cytokine levels in mock-exposed cultures. However, concentrations of endotoxin (lipopolysaccharide) as low as 0.5 ng/ml induced significant production of mRNA and protein for these three cytokines. Preincubation of mononuclear cells with "shake" HIV-1 preparations and also mock-infected shake preparations prior to lipopolysaccharide stimulation resulted in a two- to threefold increase in IL-1 beta and TNF-alpha production. This priming effect was not observed with rgp120 (0.1 to 10 micrograms/ml) or standard HIV-1 or mock-infected supernatants, suggesting the presence of biologically active material independent of virus in the shake preparations. Our studies indicate that, in the absence of endotoxin, HIV-1, HIV-2, and HIV gp120 do not induce production of IL-1 beta, IL-6, or TNF-alpha by peripheral blood mononuclear cells.
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PMID:Human immunodeficiency virus does not induce interleukin-1, interleukin-6, or tumor necrosis factor in mononuclear cells. 233 21

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) are potent immunomodulatory cytokines which are produced principally by cells of the macrophage-monocyte lineage. We conducted an investigation to assess the secretion of these cytokines by bronchoalveolar macrophages from patients with progressive stages of human immunodeficiency virus (HIV-1) infection. The mean level of TNF-alpha produced by macrophages from 9 patients with AIDS was significantly reduced compared with the responses of macrophages from 6 healthy HIV-1-seronegative persons, 6 patients with either asymptomatic HIV-1 infection or persistent generalized lymphadenopathy, and 6 patients with AIDS-related complex (ARC). The four study groups did not differ in their mean IL-1 beta responses. However, within the HIV-1-infected patient population, macrophages from 4 patients, 3 of whom had AIDS and 1 with ARC, failed to secrete detectable levels of IL-1 beta. All 4 patients were also nonresponsive in assays for TNF-alpha. These data establish that advanced HIV-1 infection may result in a pronounced dysfunction in the cytokine responses of alveolar macrophages.
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PMID:Production of tumor necrosis factor-alpha and interleukin-1 by alveolar macrophages from HIV-1-infected persons. 234 Feb 4

This study reports on the direct effect of the envelope glycoprotein (gp120) of the human immunodeficiency virus type 1 (HIV-1) on human monocyte function. Addition of preparations of purified gp120 from the HIV-1 to human monocytes resulted in the production of interleukin 1 (IL-1) and arachidonic acid metabolites from the cyclooxygenase and lipoxygenase pathways. Quantification of prostaglandin E2 (PGE2) and IL-1 revealed an increase in both mediators with 50 ng of gp120 per ml and an increase of 12- and 30- to 40-fold with 200-400 ng of gp120 per ml, respectively. Unlike native gp120, the recombinant nonglycosylated gp120 fragments PB1-RF and PB1-IIIB, as well as one of the core structural proteins of HIV-1, p24, did not increase arachidonic acid metabolism or IL-1 activity. Cytofluorometric analysis revealed that gp120 blocked the binding of OKT4A to the CD4 on monocytes, whereas OKT4 binding was unaffected. Involvement of the CD4 in signal transduction was further demonstrated by the ability of OKT4 and OKT4A monoclonal antibodies to increase monocyte PGE2, IL-1 activity, and nanogram amounts of IL-1 beta.
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PMID:Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. 253 71

Mononuclear phagocytes, including alveolar macrophages (AM), can be infected by the human immunodeficiency virus (HIV). Acting as accessory cells (AC), AM could infect CD4 lymphocytes through cell-to-cell contact and by inducing T cell proliferation, which increases lymphocyte susceptibility to infection. Using normal allogeneic T cells as responders, AM from infected individuals demonstrated an enhanced ability to stimulate a Con A and pokeweed mitogen lymphocyte proliferation assay compared with normal AM. Exogenous IL 1 enhanced the stimulation of a mitogen response by normal AM, but not from HIV-positive individuals, suggesting increased levels of this cytokine may explain the observed enhancement. However, increased IL 1 secretion by AM from HIV-infected patients could not be demonstrated, either in a bioassay or antigenically using an ELISA for IL-1 beta. Syncytia formation was observed when AM from asymptomatic HIV-positive individuals were cultured with normal T cells, suggesting viral transmission was occurring. Finally, in individual patients the stimulation of a mitogen response was inversely correlated with the CD4/CD8 ratio and total CD4 count, suggesting that enhanced AC function and CD4 cell depletion may be related in vivo. These findings indicate that enhanced AM accessory cell function is seen in HIV-infected individuals and could be a potential mechanism for CD4 cell depletion in the lung.
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PMID:Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung. 257 9

Cytokines play an important role not only for initiation of immune reactivity but also for development of tissue injury. Of 38 patients infected with human immunodeficiency virus type 1 (HIV-1) interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were identified in cerebrospinal fluid (CSF) of 22 (58%) and 16 (42%) patients, respectively. Among the IL-1 beta- and IL-6-positive CSF were eight of 15 HIV-1 patients with no clinical signs of central nervous system involvement and four of five patients with acquired immunodeficiency syndrome (AIDS) dementia complex. The presence of IL-6 was often associated with IL-1 beta and soluble interleukin-2 receptor in CSF as well as with intrathecal IgG synthesis. In none of the CSF samples tumor necrosis factor-alpha or interleukin-2 was detected.
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PMID:Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. 265 53


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