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

Bacterial lipopolysaccharides (LPS) or endotoxins are potent triggers of the cytokine (CK) cascade. These CKs are immune mediators which produce many biological effects and could play a detrimental rather than beneficial role in the host. In this review emphasis will be placed on the participation of two CKs, tumor necrosis factor [TNF-alpha and interleukin (IL-1) beta], in the pathogenetic development of HIV infection. We have found that TNF and IL-1 circulate in exaggerated amounts in the blood of HIV-infected subjects from the earliest phases of infection. Furthermore, we have observed a strict correlation between plasma LPS and IL-1 beta levels, thus indicating that endotoxins could account for the production of CKs in the course of HIV infection. Finally, the demyelinating role of TNF-alpha either in experimental models or in the course of AIDS dementia complex is outlined.
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PMID:HIV-infection and in vivo lipopolysaccharide-induced release of cytokines. An amplified mechanism of damage to the host. 189 85

Cells of the monocyte-macrophage lineage are important targets of HIV infection. We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor alpha (TNF alpha) is associated with expression of nuclear factor kappa B (NF-kappa B). In parallel with such differentiation, HIV transcription, monitored using an HIV long terminal repeat reporter gene construct, is activated in such cells under the influence of enhanced NF-kappa B expression. Also, in a promonocyte cell line chronically infected with HIV, NF-kappa B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF alpha. Thus, stimulation of monocyte cell lines by phorbol esters or TNF alpha induces cell differentiation and activates HIV transcription. Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages.
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PMID:Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression. 189 45

Cells from the human monocytic cell-line THP1 were incubated prior to activation with IFN-gamma or LPS with varying amounts of p24, the main product of the HIV gag gene and the major component of the virus core. The IFN-gamma-dependent increase of mRNA for HLA-DR and for the heavy chain of cytochrome b was markedly decreased by p24 but not by gp120. This effect was abrogated by anti-p24 antibodies. On the other hand, preincubation of THP1 cells with p24 did not affect the accumulation of the LPS-dependent mRNA for TNF alpha and IL1-beta. These results indicate that p24 at concentrations similar to those found in the serum of HIV-infected individuals specifically affects IFN-gamma-induced activation markers.
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PMID:The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1. 190 83

We have evaluated the TNF production by alveolar macrophages (AM) in 43 HIV-infected subjects in relation with 1) their clinical and biologic status; 2) the presence of lung opportunistic infections (OI); and 3) the expression of HIV by AM. This production was assessed in a standard chromium release test, using monocytic U937 cells as targets. The spontaneous TNF production by AM from patients without lung OI was higher than that from seronegative controls (p less than 0.02). This production by AM was similar to that of blood monocytes, suggesting that it was not related, in these subjects, to any particular lung status. The extent of TNF release by AM was correlated to the presence of a lymphocytic alveolitis (p less than 0.05), and not to the patients' clinical presentation nor to their CD4 cell count. Finally, AM from these subjects could be normally stimulated in vitro by IFN-gamma. On the other hand, it appeared that the spontaneous TNF release by AM shown in vitro to express HIV (p24+ AM) was significantly higher than that by their p24- counterparts (p less than 0.05) and by controls (p less than 0.01). In addition, contrasting with the marked increase of TNF release by p24- AM after their stimulation with IFN-gamma (p less than 0.001), p24+ AM appeared to be refractory to any stimulation by IFN, arguing for their activation in vivo. Finally, the spontaneous TNF release by AM was significantly increased during lung OI, compared with controls (p less than 0.01) as well as with AIDS patients without OI (p less than 0.01). In addition, the production of TNF by AM in these subjects was higher than that by the corresponding blood monocytes (p less than 0.02), suggesting a compartmentalization of this response within the lungs. In conclusion, it appears that the TNF production by AM of seropositive patients is highly related to the presence of lung OI as well as to the expression of HIV by these cells. In the context of the up-regulation of HIV expression induced by TNF in vitro, our data could suggest that the in vivo release of TNF by AM could participate in viral dissemination. Moreover, we hypothesize that the generation of activated AM refractory to any further stimulation could in turn lead to the development of additional pulmonary infections.
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PMID:Tumor necrosis factor production in HIV-seropositive subjects. Relationship with lung opportunistic infections and HIV expression in alveolar macrophages. 190

HIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.
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PMID:Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. 190 60

Trans-activating activities of certain cellular promoter/enhancer genes may reflect the underlying mechanism for cellular differentiation. We have used two promonocytic leukemia cell lines, U937 and HL-CZ, which differ in their differentiation antigen expression. While both cell lines express CD15 antigen, only the former expresses both CD4 and CD10 antigens. These phenotypes suggest that these two cell lines appear to be arrested at different stages of differentiation. Some regions of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1) contain nucleotide sequences which bind cellular trans-activating factors such as NF-kappa B and Sp1. These sequences are also present in cellular regulatory gene sequences. The cell lines have been transfected by electroporation with a nested series of deletion mutants containing different lengths of the promoter/enhancer region for HIV-LTR. The promoter/enhancer region has been linked to a 'reporter' chloramphenicol acetyl transferase (CAT) gene. We have found that promoter/enhancer trans-activation is markedly enhanced by treating transfected cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), while similar treatment with tumor necrosis factor-alpha (TNF alpha) slightly enhanced activation. U937 cells always showed much greater transactivating activities than did HL-CZ cells. Deletion of a negative regulatory element (NRE) from the LTR resulted in an enhanced transactivation, while deletions affecting NF-kappa B and/or Sp1 binding sites markedly reduced transactivation. Deletion of both NRE and NRF, a second negative regulatory factor binding site, from the LTR restored the transactivation. However, in the presence of TPA, deletion of NRE sequence without concomitant deletion of the downstream NRF binding sequence was sufficient for recovering transactivation. Since these two cell lines have shown subtle differences in these responses, it may be speculated that monocytes at different stages of differentiation may respond in different ways, qualitatively and/or quantitatively, to signal transduction factors involved in the transactivation of cellular genes.
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PMID:Regulation of cellular trans-activating activities in two different promonocytic leukemia cell lines. 191 29

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

30 patients with HIV infection were enrolled to evaluate the clinical efficacy and toxicity of zidovudine (AZT), 0.5 g/day p.o. (Group A) vs. AZT 0.5 g/day p.o. plus intravenous immunoglobulins (IVIG), 0.4 g/kg of body weight for three consecutive days, followed by one treatment of 0.6 g/kg of body weight every fourth week (Group B), over a period of one year. The study was open and randomized. The treatment groups were compared using the following study variables: 1) type of infections, recurrences and severity; 2) change in CD4+ T and CD8+ T cell count; 3) change in platelet count; 4) change in TNF alpha serum levels; 5) the probability of not developing an opportunistic infection over a period of 12 months. Patients from Group B developed less pathological events in comparison to Group A. No significative differences were evident with regard to values of T cell subsets obtained before and after treatment in each group and between the two groups. On the contrary, in 12 out of 15 patients from Group B there was a significant increase in platelet count. In both groups there was a significant decrease of mean serum levels of TNF alpha when a comparison was made between time 12 vs. time 6. However, when data were expressed as single values, in three subjects from Group B TNF alpha was still detectable by time 12 vs. 9 individuals in Group A. The cumulative probabilities of developing an opportunistic infection over the 12 months of treatment in the Group A subjects were significantly higher than in the Group B subjects (p less than 0.01). Adverse effects--nausea and gastric pain--were reported for 3 individuals (20%) from Group A and 4 patients (26%) from Group B. In conclusion, patients treated with AZT are especially likely to benefit from IVIG prophylaxis.
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PMID:Clinical and immunologic effects of combination therapy with intravenous immunoglobulins and AZT in HIV-infected patients. 194 58

Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 to productively infect macrophages may be influenced by endogenous cytokines that alter the activation state of these cells. In this study, the effect of tumor necrosis factor-alpha/cachectin (TNF alpha), a cytokine with macrophage-activating properties, on HIV-1 replication in primary blood monocyte-derived macrophages was examined. Treatment of macrophages with recombinant human TNF alpha (rTNF alpha), starting before or after HIV-1 infection, consistently enhanced viral production fivefold or greater above control (P less than .01). rTNF alpha was active at low concentrations (0.05-50 ng/ml) and increased the replication of both lymphocyte-tropic (human T lymphotropic virus type IIIB) and macrophage-tropic (human T lymphotropic virus type III BaL) strains of HIV-1. These findings provide additional evidence that TNF alpha may play a role in the pathogenesis of HIV-1 infection by upregulating viral expression in macrophages.
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PMID:Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type 1 replication in primary macrophages. 198 79

Three human colonic epithelial cell lines, SW620, HT29, and T84, were characterized with respect to HIV-1 infection and gene expression. SW620 and HT29, but not T84, could be infected with HIV-1. CD4 messenger RNA and its protein product were identified in SW620 cells but not in HT29 or T84 cells. Anti-CD4 antibody blocked infection of SW620 cells but had no effect on infection of HT29 cells. In SW620 and HT29 cells transfected with the HIV-1 long terminal repeat (LTR) linked to the chloramphenicol acetyl transferase (CAT) reporter gene, an intact HIV-1 enhancer element was required for stimulation of CAT activity by tumor necrosis factor alpha (TNF alpha) and phorbol ester. T84 was not able to mediate a TNF alpha or phorbol ester response. These studies provide further evidence that HIV-1 can infect cells by mechanisms other than those mediated by the CD4 receptor and describe complementary models for analyzing HIV-1 infection and expression in colonic epithelial cells.
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PMID:HIV-1 infection and expression in human colonic cells: infection and expression in CD4+ and CD4- cell lines. 205 67


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