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

To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1 beta, IL-6, IL-2, and INF-gamma in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1 beta- and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1 beta- and IL-6-producing cells were present in interfollicular and follicular areas. IL-2- and INF-gamma-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of IL-1 beta, IL-6-, and IL-2-producing cells in HIV lymph nodes were not different from those found in six HIV unrelated hyperplastic lymph nodes. In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes. The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production. INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA. Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis.
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PMID:Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes. 211 24

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

We have devised a luminescence sandwich ELISA for the quantification of IL-6 in both sera and cell culture supernatants, which had a detection limit of 100 fg/ml of test sample. By using the luminescence sandwich-ELISA, low but measurable levels of IL-6 (9.5 pg/ml on average) were found in the sera from normal individuals. The serum levels of IL-6 were elevated in HIV-seropositive asymptomatic carriers (55.5 pg/ml on average), and the IL-6 levels were correlated with the degree of HIV-induced disease progression (AIDS-related complex 106.8 pg/ml on average and (AIDS 283 pg/ml). IL-6 immunoreactivity in the sera of AIDS patients eluted at a 25,000 m.w. major peak, which was biologically active and heat-stable, and a 500,000 m.w. minor peak in size-exclusion HPLC. Interestingly, a significant correlation was observed between the serum IL-6 levels and soluble IL-2R levels. In vitro, HIV infection of PHA-activated PBMC led to enhanced release of IL-6 into the culture supernatants. Moreover, soluble IL-2R release was markedly increased by adding exogenous IL-6, whereas it was decreased by adding the neutralizing anti-IL-6 mAb to the cultures. These results demonstrate that increased IL-6 levels are significantly associated with sIL-2R levels, and suggest a cause of the increased levels of this receptor in patients with HIV infection. Furthermore, both serum IL-6 and serum IL-2R levels in HIV infection reflect the stage of the HIV-induced disease.
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PMID:Quantitative analysis of serum IL-6 and its correlation with increased levels of serum IL-2R in HIV-induced diseases. 225 6

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

Polyclonal B cell activation is commonly observed in AIDS and in infection with HIV. Because IL-6 (B cell stimulatory factor 2) plays an essential role in the differentiation of activated B cells to Ig-secreting cells, and because IL-6 production is induced by exposure of human PBMC to HIV, we measured the level of circulating plasma IL-6, spontaneously-produced IL-6, and IL-6 mRNA in HIV-infected donors and in healthy control donors. Elevated levels of plasma IL-6 and IL-6 mRNA were detected in HIV-infected donors. PBMC isolated from the peripheral circulation of HIV-infected donors, and cultured without added exogenous activators of IL-6 production, produced markedly elevated amounts of IL-6 when compared with cells isolated from healthy donors. Interestingly, levels of an acute-phase protein, which is known to be induced by IL-6, was also increased in HIV-infected donors. These results demonstrate that elevated levels of IL-6 are associated with HIV-infection, and suggest that IL-6 over-production may contribute to the polyclonal B cell activation seen in AIDS and HIV infection.
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PMID:Infection with HIV is associated with elevated IL-6 levels and production. 229 99

To determine the effects of immunomodulatory agents upon HIV replication in macrophages, cultured monocyte-derived macrophages were treated with various substances and then infected with a macrophage-tropic strain of HIV-1. Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages. In treated cultures, little or no infectious HIV or p24 core antigen was released into the supernatant, no virions were seen by electron microscopy, no viral RNA or DNA was detectable in the cell lysates, and no cytopathology (as determined by multinucleated giant cell formation) occurred. In contrast, pretreatment with a wide dose range of recombinant IL-1 beta, IL-2, IL-4, IL-6, M-CSF, TNF, or lymphotoxin failed to protect macrophages from productive infection by HIV. A consistent effect of granulocyte/macrophage-CSF on HIV replication in macrophages was not observed. In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely. In kinetic studies, IFN-alpha, IFN-gamma, or LPS were added to the macrophage cultures either before or after infection with HIV. Even when added 3 d after infection with a multiplicity of 1 50% tissue-culture infectious dose per cell, all three treatments markedly reduced virion release, suggesting that these agents act at a point in the viral life cycle beyond the early events of virus binding, penetration, and uncoating. These data indicate that HIV replication in previously uninfected macrophages may be regulated by an inducible host cell mechanism. These findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for interferons in the therapy of HIV infection.
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PMID:Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. 246 37

Among the cytokines tested here (IL-2, IL-3, IL-4, IL-5, IL-6, granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), interferon-alpha (IFN-alpha), interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma] only interleukin 1(IL-1) augmented HIV-long terminal repeat(LTR) directed chloramphenicol acetyl transferase(CAT) activity in protein kinase C(PKC)-independent manner. However, a stimulation by IL-1 was not as efficient as that due to tumor necrosis factor and the HIV production was not significant. IL-1 was not cytotoxic to MOLT-4/HIV cells.
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PMID:Effect of interleukin-1 on the augmentation of human immunodeficiency virus gene expression. 248 Jul 82

AIDS dementia complex (ADC) is a complex, progressive neuropsychiatric syndrome seen in 60-70% of the patients with AIDS. The structural and functional changes associated with ADC may be the result of a variety of indirect mechanisms mediated via activated brain cells or/and virus that produce neurotoxins including N-methyl-D-aspartate receptor agonist (eg, quinolinic acid, glutamate), cytokines, gp 120 and nitric oxide. The level of the neurotoxin and kynurenine pathway metabolite, quinolinic acid, is increased in the brain and CSF of HIV-1-infected patients, and is correlated with quantitative measures of neurologic impairment. Importantly, increased CSF and brain levels of QUIN also occur in other inflammatory neurologic diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicemia), independent of HIV-1 infection. Therefore, QUIN and other neuroactive kynurenine pathway metabolites may be final common mediators of neurologic dysfunction in a broad spectrum of inflammatory neurologic diseases. Conversion of L-tryptophan to QUIN has also been demonstrated in vitro in both brain tissue following macrophage infiltration, and in macrophages stimulated by interferon-gamma or HIV infection. Macrophages in vitro have a high capacity to synthesize QUIN following exposure to interferon-gamma, tumor necrosis factor-alpha, IL-1 beta and IL-6, compared to cells derived from other tissues. Notably, the concentrations achieved in the macrophage incubates exceeded the levels found in the CNS of HIV-1-infected patients, and exceeded the concentrations shown to be neurotoxic in vitro. We hypothesize that increased kynurenine pathway metabolism following inflammation reflects the presence of macrophages and other reactive cell populations at the site of brain infection. Strategies to attenuate the neurotoxic effects of kynurenines, such as inhibitors of kynurenine pathway metabolism and cytokine antibodies may offer new approaches to therapy.
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PMID:[Biochemical studies on AIDS dementia complex--possible contribution of quinolinic acid during brain damage]. 747 52

As an attempt to elucidate the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-related cytopenia, the effects of infection of long-term primary bone marrow culture (LTBMC)-derived adherent cells on hematopoiesis were investigated. Productive infection could then be established only when using monocytotropic strains HIV-1Ba-L, HIV-1Ada, and HIV-1JR-FL but not with lymphocytotropic strain HIV-1LAI. Culture supernatants were tested for major cytokines involved in the regulation of hematopoiesis: neither IL-3 nor GM-CSF were detectable in the infected or noninfected cultures; in contrast, TGF-beta, TNF-alpha, MIP-1 alpha, Steel Factor, and IL-6 were detected at all times in established LTBMCs, but their levels were not consistently altered by virus replication. In vitro functional analysis by colony and long-term culture assays showed that HIV-1 infection failed to alter either the kinetics or the number of hematopoietic progenitors produced by the stromal layers; it did not interfere with the clonogenicity of exogeneous CD34+ cells in semisolid assays, and no difference was observed relative to the controls when HIV-1-infected stromal layers were tested for their ability to sustain long-term hematopoiesis. These results show that productive and sustained virus replication in the macrophage component of LTBMCs does not significantly alter the profile of major cytokines involved in regulating hematopoiesis, nor is it sufficient by itself for altering in vitro hematopoiesis under the baseline conditions used.
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PMID:In vitro infection of bone marrow-adherent cells by human immunodeficiency virus type 1 (HIV-1) does not alter their ability to support hematopoiesis. 748 69

HIV-infected patients exhibit defects in B cell differentiation and in the IL-6 response of B cells, in association with autoantibody formation against T cells. These autoantibodies have been implicated as important factors in the development of immunodeficiency disease. As the restoration of defective B cell responses might prevent autoantibody formation and the resulting immunosuppression, we studied whether in vitro treatment with recombinant IL-2 (rIL-2), recombinant IL-4 (rIL-4) or recombinant IL-6 (rIL-6) might restore the response of B cells of HIV-infected patients. B cells of 6 HIV-negative hemophilia patients, 4 HIV-positive patients at CDC stage II, III, 4 HIV-positive patients at CDC stage IV, and 6 healthy controls were tested in Staphylococcus aureus Cowan I (SAC-I)-stimulated B cell cultures and Pokeweed mitogen (PWM)-stimulated allogeneic B and T cell cocultures. B cell differentiation was assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG and IL-6 in culture supernatants. In vitro application of rIL-6 resulted in suppression of both elevated unstimulated and mitogen-stimulated B cell responses in a dose-dependent manner which was in part due to feedback inhibition. PWM- and SAC-I-stimulated IgG and IgM responses, respectively, could be restored after addition of 10 U/ml rIL-2 in HIV-negative patients, but not in HIV-positive patients. Addition of rIL-4 to cultures resulted in suppression of both unstimulated and mitogen-stimulated IL-6 secretion and B cell responses. Severely depressed B cell responses in CDC IV patients were not significantly affected by cytokine application. These results indicate that defective Ig responses in HIV-negative patients may be restored by rIL-2 treatment whereas HIV-induced B cell defects are not corrected by supply of T cell help or cytokines promoting B cell growth and differentiation.
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PMID:In vitro cytokine treatment of B cell defects in HIV-infected hemophilia patients. 748 89


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