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

The effects of long-term zidovudine treatment on functional parameters of cell-mediated immunity were investigated in 15 symptomatic HIV-antibody-positive patients with clinical evidence of opportunistic infections. Mononuclear leukocytes were obtained before administering the drug, and after 3 and 6 months of treatment. The cells were stimulated with lectins in order to assess variations of mitogen-induced lymphocyte proliferation and production of gamma-interferon (IFN) and interleukin-2 (IL-2), and with Newcastle disease virus (NDV) to assess variations of alpha-IFN production. Mean proliferative responses to PHA and Con-A did not show any significant change between baseline, 3 months, and 6 months values (25,158 +/- 11,763, 24,662 +/- 8,955, and 34,924 +/- 16,283 D-cpm, respectively, for PHA, p greater than 0.05; and 5,470 +/- 1,890, 4,953 +/- 2,518, and 4,539 +/- 3,286 D-cpm, respectively, for Con-A, p less than 0.05). Mean response to PWM (9,707 +/- 4,429 D-cpm at entry) increased significantly after 3 months, but returned to baseline values at 6 months (17,039 +/- 5,123 and 10,314 +/- 3,855 D-cpm, respectively, p = 0.016). IL-2 production (5.51 +/- 4.0 I.U. at entry) rose particularly at 3 months and persisted at the same levels at 6 months (9.6 +/- 4.8 and 9.5 +/- 6 I.U., respectively, p less than 0.05). By contrast, a moderate but significant decrease in gamma- and alpha-IFN production was observed (65 +/- 2.2, 35.1 +/- 1.6, and 22 +/- 2 I.U., respectively, for gamma-IFN, p less than 0.05; 60 +/- 3, 64 +/- 2.6, and 12 +/- 1.5 I.U., respectively for alpha-IFN, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of long-term zidovudine treatment on cell-mediated immune response and lymphokine production. 170 62

Every step in the replication cycle of HIV provides unique opportunities for controlling the progression of AIDS. In this regard, virus protein synthesis should be an important target for limiting HIV multiplication in cells. Molecular mechanisms in the regulation of HIV protein synthesis were therefore investigated in the context of interferon action. The interferon-inducible enzymes, 2-5A synthetase and dsRNA-dependent protein kinase, which can inhibit translation were activated by HIV-1 leader RNA. In cell-free systems, leader RNA and Tat protein of HIV inhibited and enhanced translation, respectively. An intriguing interplay of these viral and host factors were shown to influence the rate of translation in vitro. A model describing opposing actions of HIV Tat protein and interferon in HIV replication is represented.
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PMID:Translational regulation by HIV leader RNA, TAT, and interferon-inducible enzymes. 170 18

Cytokines including interferon (IFN) and tumor necrosis factor (TNF) are potent modulators of immune processes. They are synthesized in response to microbial infections and inflammation. TNF and IFN interact with other cytokines to elicit differentiation and cellular responses of specific target cells. In view of their multiple biological effects, we have postulated that dysregulation of IFN and TNF may contribute to the pathogenesis of HIV infection. Here, we review data showing that the expression of IFN-alpha receptors is down-regulated in patients with AIDS. As a consequence, HIV-infected cultured cells and cells from AIDS patients show hyporesponsiveness to IFN action. This could contribute to mechanisms by which HIV evades the antiviral activity of IFN-alpha in HIV-infected cells and raise the question of the usefulness of IFN-alpha in the treatment of end-stage AIDS. TNF is a major mediator of inflammation and sepsis and also is capable of inducing the replication of HIV. TNF synthesis and its receptor expression are upregulated by the acid-labile IFN-alpha subtype present in the sera of HIV-infected individuals. In addition, the acid-labile IFN present in AIDS sera may contribute to the pathophysiological changes in sepsis by rendering the cells from AIDS patients hypersensitive to endotoxin stimulation resulting in further synthesis of TNF. Thus aberrant regulation of these cytokines and their cognate receptors are likely contributing factors to the pathogenesis of AIDS.
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PMID:The role of interferon and tumor necrosis factor in the pathogenesis of AIDS. 170 66

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.
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PMID:The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. 171 6

An in vitro model of interferon (IFN) induction in HIV infection was established. IFN are induced by a cooperative mechanism, involving monocytes/macrophages (M/M) as well as lymphocytes. M/M non-lytically infected with HTLV-IIIB did not produce IFN, but were able to induce high titres of IFN activity when cocultured with peripheral blood lymphocytes, cell-cell contact being required. IFN alpha as well as IFN gamma were induced, as shown by neutralization with specific antisera. The antiviral activity of HIV-induced IFN was shown by infectivity reduction assays, and the immune-modulating capacity was demonstrated by activation of M/M leading to neopterin release.
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PMID:Interferon induction by cell-cell interaction of HIV-infected monocytes/macrophages with lymphocytes. 171 79

To further document the role of interferons in the restriction of HIV1 replication in cells of the monocyte/macrophage lineage, the antiviral effects of alpha-interferon (IFN alpha) were studied in chronically HIV 1-infected promonocytic cells U937, in which IFN alpha was endogenously produced or to which recombinant IFN alpha was added. Protein analysis performed after immunoprecipitation of culture media revealed that the addition of anti-IFN alpha antibody led to an increase in the production of viral particles, whereas addition of IFN alpha caused its decrease in a dose-dependent manner, indicating that IFN alpha mainly affects viral assembly and virion release. However, the treatment of HIV 1-infected cells with IFN alpha did not cause an increase in the amount of intracellular viral proteins, suggesting that this cytokine might act on other steps in the viral life cycle. No decrease in the level of the 3 main types of viral RNA was observed by Northern blot analysis, indicating that proviral transcription was not restricted by IFN alpha. Furthermore, cotransfection experiments with TAR(trans-activation responsive)-element-containing expression plasmids demonstrated that viral replication appears to be restricted at either a post-transcriptional and/or a translational level. These experiments suggest that the double-stranded (ds) inverted repeat TAR sequence present in HIV1 leader RNA may inhibit viral protein synthesis by phosphorylating the dsRNA-activated protein kinase induced by IFN. These results provide an impetus for achieving antiretroviral therapy based on the constitutive expression of IFN in monocytes and macrophages.
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PMID:Interferon-regulated viral replication in chronically HIV1-infected promonocytic U937 cells. 171 78

Facial Kaposi's sarcoma is a severe psychological problem for HIV-infected patients if systemic chemotherapy or interferon therapy is not possible. To help these patients, it is important to offer a palliative treatment that is suitable for outpatients and is not complicated by severe side-effects but still yield satisfactory cosmetic results. A total of 65 patients with 216 facial Kaposi's sarcomas were treated with cryosurgery (92 tumours, 29 patients), intralesional chemotherapy with vincristine (28 tumours, 12 patients), radiotherapy (87 tumours, 15 patients) and camouflage (multiple tumours, 9 patients). Cryosurgery is the treatment of choice for small (less than 1 cm) macular or slightly nodular Kaposi's sarcoma. Larger nodular tumours are better treated by intralesional chemotherapy (single doses of 0.01-0.1 mg vincristine per tumour) or low-dose radiotherapy (3-4 x 4 Gy). These palliative treatment methods are not indicated in cases of rapid tumour progression and dissemination; in such cases, camouflage (covering the tumours with water-resistant make-up) is helpful as a local palliative measure.
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PMID:[Facial kaposi's sarcoma. Palliative treatment with cryotherapy, intralesional chemotherapy, low-dose roentgen therapy and camouflage]. 171 2

Tryptophan (Trp) is an indispensable amino acid required for biosynthesis of proteins, serotonin and niacin. Indoleamine 2,3-dioxygenase (IDO) is induced by infections, viruses, lipopolysaccharides, or interferons (IFNs) and this results in significant catabolism of Trp along the kynurenine (Kyn) pathway. Intracellular growth of Toxoplasma gondii and Chlamydia psittaci in human fibroblasts in vitro is inhibited by IFN-gamma and this inhibition is negated by extra Trp in the medium. Similarly, growth of a number of human cell lines in vitro is inhibited by IFN-gamma and addition of extra Trp restores growth. Thus, in some in vitro systems, antiproliferative effects of IFN-gamma are mediated by induced depletion of Trp. We find that cancer patients given Type I or Type II IFNs can induce IDO which results in decreased serum Trp levels (20-50% of pretreatment) and increased urinary metabolites of the Kyn pathway (5 to 500 fold of pretreatment). We speculate that in vivo antineoplastic effects of IFNs and clinical side effects are mediated, at least in part, by a general or localized depletion of Trp. In view of reported increases of IFNs in autoimmune diseases and our earlier findings of elevated urinary Trp metabolites in autoimmune diseases, it seems likely that systemic or local depletion of Trp occurs in autoimmune diseases and may relate to degeneration, wasting and other symptoms in such diseases. We find high levels of IDO in cells isolated from synovia of arthritic joints. IFNs are also elevated in human immunodeficiency virus (HIV) patients and increasing IFN levels are associated with a worsening prognosis. We propose that IDO is induced chronically by HIV infection, is further increased by opportunistic infections, and that this chronic loss of Trp initiates mechanisms responsible for the cachexia, dementia, diarrhea and possibly immunosuppression of AIDS patients. In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin. In preliminary studies, others report low levels of Trp and serotonin, and elevated levels of Kyn and quinolinic acid in AIDS patients. The implications of these data in cancer, autoimmune diseases and AIDS are discussed.
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PMID:Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 172 46

The remarkable ability of HIV to insinuate itself into the working of the immune system is the key of its success as an infectious agent. Given that the cytokine network regulates the immune responses, it is not surprising that cytokines can modulate HIV infection. GM-CSF, IL6 and TNF-alpha enhance HIV, but TGF-beta and HIF inhibits the virus. However, the anti-HIV activity of TGF-beta is restricted to myeloid cells, while HIF inhibits HIV in myeloid cells and in T-lymphocytes. HIF is produced by CEM cells after induction by an extract from pine cones. It is not an interferon and is likely a novel cytokine. It is pepsin-sensitive but trypsin-resistant and has an apparent molecular weight of 7-12 KDa. Apart from having anti-HIV activity, crude preparations of HIF also inhibit HTLV-1 virus but not HSV virus replication.
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PMID:Cytokine regulation of the human immunodeficiency virus (HIV). 172 85

In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages.
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PMID:Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. 173 92


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