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

Tumor necrosis factor-alpha (TNF-alpha) induces the expression of human immunodeficiency virus type-1 (HIV-1) in vitro in chronically infected cells of T and monocytic origin. The tat protein from the HIV-1 virus has been shown to be essential for HIV replication and in the immunosuppression associated with the virus infection. Previous studies in our laboratory have shown that HIV-1 tat gene induces TNF-beta (lymphotoxin) in human B-lymphoblastoid cells (Sastry et al., 1990, J. Biol. Chem. 265, 20091-20093). In an attempt to characterize further the relationship between the host and HIV-1, we investigated the effect of the functional HIV-1 tat gene on the expression of TNF receptors in a human B lymphoblastoid cell line (Raji). We report here that Raji cells transfected with HIV-1 tat gene express fewer cell surface TNF receptors than control cells. At least a 5-fold decrease in the receptor number without any significant change in receptor affinity was observed. The decrease in TNF receptors in tat-transfected Raji cells (Raji-tat cells) was found not to be due to receptor occupancy by the autocrine production of TNF-beta. The decrease in the cell surface expression of TNF receptors in Raji-tat cells was also found to be not due to a decrease in the gene expression of the receptor. The kinetics, amount of TNF binding and its internalization were temperature dependent, and it was different in Raji-tat cells than in the control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphokine Cytokine Res 1992 Dec
PMID:Down-modulation of cell surface expression of p80 form of the tumor necrosis factor receptor by human immunodeficiency virus-1 tat gene. 133 62

Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) are not constitutively produced by human mononuclear phagocytes. In the present study we have investigated the production of these cytokines in human blood-derived macrophages (BDM) after infection with 16 primary HIV-1 blood isolates obtained from individuals at different stages of disease. In addition, we monitored the replicative capacity of these primary isolates in blood-derived macrophages over a 3-month period. Production of IL-1 alpha was detected in two cultures, IL-beta was positive in two other cultures, and both IL-1 alpha and IL-beta were present in three additional macrophage cultures. IL-1 alpha production was also detected in BDMs infected with the laboratory strain HIV-1 IIIB. In contrast, TNF-alpha was not found in any of the culture supernatants tested. All primary HIV-1 isolates used in these experiments were able to infect BDM productively irrespective of the clinical stage of the patients at the time of virus isolation. The production of IL-1 was mostly found in chronically infected cultures displaying low levels of HIV-1 replication. These results indicate that macrophages tropism is a general feature of all HIV-1 isolates. Furthermore, release of IL-1 by mononuclear phagocytes upon HIV-1 infection may contribute to the pathogenesis of HIV-1 related diseases.
Cytokine 1992 May
PMID:Blood-derived macrophages produce IL-1, but not TNF-alpha, after infection with HIV-1 isolates from patients at different stages of disease. 149 53

The production of TNF-alpha and TNF-beta by human B-cell lines was studied at both the molecular and biological levels. The 24 B-cell lines studied included EBV+ cell lines (n = 13), EBV- cell lines (n = 8), and AIDS-associated B-cell lines (AABCL) (n = 3) which are EBV+/HIV-. Whereas radioimmunoprecipitation using TNF-alpha antisera detected 17-kDa TNF-alpha as expected, similar studies with anti-TNF-beta antisera revealed TNF-beta microheterogeneity. In the AABCL three bands with approximate MW of 26, 24, and 22 kDa were detected under reducing conditions, and in the non-AABCL, two bands only with 26 and 22 kDa were observed. To determine whether the size heterogeneity of TNF-beta is due to glycosylation, TNF-beta deglycosylation studies were done in two AABCL (PA682BM-2, PA682PE-1) and one non-AABCL (IM-1178). As control, the normal lymphoblastoid B-cell line RPMI-1788, which is known to secrete TNF-beta with MW 25 and 20 kDa, has been used. Deglycosylation studies using N-glycanase + neuraminidase + O-glycanase reduced the various bands in all cell lines to one band with 18.6 kDa, which is compatible with the TNF-beta backbone. In attempt to determine whether the differential glycosylation of TNF has any functional significance, all 24 cell lines were studied for TNF secretion and for TNF neutralization by monoclonal antibodies and polyclonal antibodies to TNF-alpha and TNF-beta. Constitutive secretion of TNF-alpha and TNF-beta has been detected only in the three AABCL. Following activation with the tumor promoter teleocidin, the secretion of both TNFs has been triggered in 2/8 EBV- cell lines and in 8/13 EBV+ non-AABCL. Using rabbit polyclonal antibodies to human TNF-alpha and to human TNF-beta, only little if any neutralization of these TNFs has been shown. Our data suggest that the differences in glycosylation of B-cell-derived TNFs may account for the incomplete neutralization, and may influence the cytotoxic biological activity of this lymphokine.
Lymphokine Cytokine Res 1992 Feb
PMID:Human B-cell TNF-beta microheterogeneity. 157 46

Macrophage infiltration is a constant feature of human virus-infected tissues. However, the in situ functional status of these cells remains undetermined. In order to document an activation of macrophages in virus-infected tissues, the expression of IL-1 beta and IL-6 genes was analyzed using in situ hybridization. Several tissues were studied, as well as infections induced by different viruses: lymph nodes infected by HIV-1 (9 cases) or EBV (one case), lungs infected by CMV (5 cases) or adenovirus (1 case), livers infected by HBV, either chronically (2 cases) or acutely (7 cases presenting a fulminant hepatitis). With the exception of fulminant HBV hepatitis, IL-1 beta and IL-6 genes were expressed in all cases. IL-1 beta and IL-6 genes were usually coordinately regulated, as cells containing IL-1 beta or IL-6 mRNA were present in identical amounts and displayed a similar distribution. Analysis of the location and the morphology of monokine gene-expressing cells indicated that both small macrophages and endothelial cells expressed IL-1 beta and IL-6 genes. However, neither tingible body macrophages present in lymph node follicles nor Kupffer cells expressed these genes at a detectable level. Infected cells themselves were also negative for monokine gene expression. These findings indicate that expression of IL-1 beta and IL-6 genes by reactive cells may play a role in viral spreading limitation as well as virus-induced tissue damage.
Eur Cytokine Netw
PMID:In vivo expression of IL-1 beta and IL-6 genes during viral infections in human. 165 44

Peripheral blood monocytes (PBM) can selectively lyse malignant or virus-infected cells. We investigated the effects of target cell infection with HIV-1 on PBM cytolytic function. Cytokine-activated PBM lysed uninfected, HSV-1-infected or vaccinia virus-infected tumor cells, but did not lyse the same cell lines when infected with the human immunodeficiency virus type 1 (HIV-1). HIV did not impair PBM viability, and actinomycin D (Act D) pretreatment of HIV-infected target cells restored their susceptibility to PBM-mediated lysis. Either antibody to CD4 (Leu3a) or a recombinant vaccinia virus that induces expression of the HIV envelope protein, also inhibited target cell lysis by PBM. These studies indicate that CD4 can function as a mediator of PBM cytolytic function, and that target cell expression of the HIV-1 envelope protein may inhibit monocyte-mediated antitumor responses.
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PMID:Monocyte-mediated lysis of HIV-infected tumor cells. 169 72

The capacity of human monocytes/macrophages (M/M) infected with a human immunodeficiency virus-1 (HIV-1) isolate to produce several immunomodulating cytokines including interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage chemoattractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1 beta, TNF-alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M. The impact of the role of these cytokines in the immunity and pathogenesis of HIV-1 infection is discussed.
Lymphokine Cytokine Res 1991 Dec
PMID:Decrease in cytokine production by HIV-infected macrophages in response to LPS-mediated activation. 172 30

Several immunological abnormalities were detected in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected children. Intrathecal synthesis of immunoglobulins, free light chains (FLC), IL-1 beta, IL-6, and M-CSF were demonstrated both in asymptomatic children and children with subacute encephalopathy. Our findings further support the hypothesis that an immunopathological subclinical process within the central nervous system (CNS) may be an early manifestation of acquired immunodeficiency syndrome (AIDS). Cytokine detection in the CSF may represent a useful diagnostic tool in evaluating the outcome of HIV-1-infected patients.
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PMID:Immunological markers in the cerebrospinal fluid of HIV-1-infected children. 186 84

We have measured the production of interleukin 1 (IL 1), interleukin 6 (IL 6), and tumor necrosis factor alpha (TNF alpha) by unstimulated monocytes and monocytes stimulated with lipopolysaccharide (LPS) isolated from the peripheral blood of patients infected with human immunodeficiency virus 1 (HIV-1) and healthy controls. Spontaneous and LPS-induced cytokine production were not significantly different between patients and controls. Median lipopolysaccharide-stimulated cytokine secretion for patients and controls was 1.7 and 4.3 U/ml for IL 1, 475 and 625 U/ml for IL 6, and 468 and 580 pg/ml for TNF alpha. Cytokine levels were not related to stage of disease. We conclude that in vivo HIV infection itself does not alter peripheral blood monocyte cytokine secretion.
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PMID:Cytokine secretion by peripheral blood monocytes from human immunodeficiency virus-infected patients is normal. 193 24

We have examined the effect and potential mechanism of Cyclosporin A (CsA) on the Interleukin-2-receptor alpha chain (IL-2R alpha) expression in human T-lymphocytes. CsA pretreatment of PHA-activated T-cells led to 30-50% decrease in Tac antigen surface expression and a concomitant decrease in the steady state IL-2R alpha mRNA levels. Transacting factors which recognize a kB-like sequence present in the IL-2R alpha chain regulatory region have been suggested to participate in the transcriptional regulation of the IL-2R alpha gene. Using oligonucleotides corresponding to the 5' regulatory region of the IL-2R alpha gene (i.e. 245 to 291 bp upstream of the start codon) and nuclear extract from resting T lymphocytes, we detected two specific bands by gel mobility shift assay. One of these bands is specifically increased after stimulation with phytohemagglutinin (PHA) and it is inhibited by CsA pretreatment. The same pattern of binding activity has been observed with the tandem repeat of NF-kB binding site present in the enhancer element of the human immunodeficiency virus long terminal repeat (HIV-1 LTR). These data suggest that CsA affects IL-2R receptor alpha chain expression by inhibiting the interaction of transacting factors to kB-like sequences after PHA activation. These findings may be of some relevance for the understanding of the immunosuppressive effects of CsA in normal human T lymphocytes.
Eur Cytokine Netw
PMID:Cyclosporin A inhibits induction of IL-2 receptor alpha chain expression by affecting activation of NF-kB-like factor(s) in cultured human T lymphocytes. 212 97

Dehydration-rehydration liposome vesicles (DRVs) containing various cytokines were evaluated for their ability to induce delayed-type hypersensitivity (DTH) and humoral immunity to the recombinant envelope protein rgp120 of the MN strain of human immunodeficiency virus type 1 (HIV-1). The DRVs trapped approximately 25% of the radiolabeled cytokines and approximately 17% of the radiolabeled rgp120 that were added. The level of trapping was greater than the aqueous volume of the DRVs, indicating association of the proteins with the lipid bilayer. Flow cytometric analysis using antibody to rgp120 or the V3 loop of rgp120 showed the diameter of the DRVs to be 2-7.5 microns. Transmission electron microscopy confirmed the heterogeneity in size of the DRVs and revealed morphological heterogeneity. Transmission electron microscopy with immunogold labeling also revealed the presence of rgp120 on the surface of the DRVs. In vitro bioassays demonstrated slow leakage of biologically active cytokines from DRVs soaked in tissue culture medium containing serum. Mice injected subcutaneously three times at 14-day intervals with DRVs containing 15 micrograms of rgp120 plus interleukin 6 (IL-6) or interferon gamma (IFN-gamma) produced significantly greater DTH responses than mice injected with DRVs containing rgp120 alone. Soluble rgp120 plus soluble IFN-gamma produced DTH in some experiments, but of lower magnitude than the comparable DRVs. Interleukin 6, but not IFN-gamma, increased the antibody titer to rgp120 when included in the DRVs. The mice did not develop antibodies to IFN-gamma or IL-6. Induction of DTH by vaccines may increase protection from viral pathogens such as HIV. Cytokine-containing liposomes may be an effective adjuvant for the induction of a DTH response to envelope-antigen subunit vaccines.
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PMID:Cytokine-containing liposomes as adjuvants for HIV subunit vaccines. 749 39


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