Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the replication of human immunodeficiency virus (HIV) and HIV-induced interferon (IFN) production in human mononuclear phagocytes at 2 different stages of in vitro maturation. Blood monocytes and monocyte-derived macrophages from 6 healthy, HIV-seronegative donors were challenged with HIV1IIIB and HIV2ROD. Freshly separated monocytes produced IFN when inoculated with both HIV types. In these cultures, an inverse correlation was observed between the amount of IFN production and the rate of HIV replication. In contrast to the monocytes, 5-day-old monocyte-derived macrophages did not produce IFN when challenged with HIV, but a significant replication of HIV1IIIB and HIV2ROD was found in all cultures.
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PMID:Differential HIV replication and HIV-induced interferon production in mononuclear phagocytes: relationship to cell maturation. 172 99

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

Chronic granulomatous disease is a rare, primary immunodeficiency associated with serious bacterial and fungal infections caused by phagocytic defects of oxidative metabolism. To date the mainstay of management has been aggressive treatment of infections and the use of prophylactic antibiotics. Two patients, who showed remarkable clinical improvement when treated with recombinant gamma interferon, are reported. Both have been on treatment for at least 18 months and have continued to thrive and remain free of infections.
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PMID:Treatment of chronic granulomatous disease with recombinant gamma interferon. 173 29

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

Although 3'-azido-3'-deoxythymidine (zidovudine, AZT) has demonstrated efficacy in the treatment of human immunodeficiency virus (HIV) infection, there are limitations associated with its use. Consequently, other agents, such as 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), are being assessed for the treatment of patients with HIV infection. However, the most effective therapy for HIV infection may be combination therapy with zidovudine and any of a number of other therapies. To obtain maximum efficacy, combination regimens should include agents that do not share cross-resistance, have different mechanisms of action, and have different dose-limiting toxicities; the relative merits of a concurrent dosage schedule (limits drug failure) and a consecutive dosage schedule (limits toxicity) must also be considered. In addition, the shift between administering a starting regimen and a rescue regimen should be based on time on therapy, disease breakthrough, or drug complication. Eventually, the shift may be precipitated by the in vitro resistance patterns of individual viruses, as is now the case with antibiotics for infection. Several trials are currently in progress to assess combination therapy with zidovudine and ddC; initial results indicate that the combination may allow for improved efficacy and decreased side effects, compared with treatment with either drug alone. Trials of combination therapy with ddI, interferon alfa, and acyclovir are also in progress. It is hoped that these initial studies will pave the way for rational drug sequencing in the treatment of patients with acquired immunodeficiency syndrome.
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PMID:Treatment of AIDS with combinations of antiretroviral agents. 185 Jan 92

We performed an immunoperoxidase study on muscle biopsy specimens from 19 patients with polymyositis who were seropositive for human immunodeficiency virus (HIV) (21 specimens) and 5 HIV-seronegative patients with polymyositis and compared the findings. A quantitative analysis of T cells and T-cell subsets, B cells, natural killer cells, interleukin-2 receptor-positive cells, and macrophages was performed on serial sections from all the specimens. Localization of major histocompatibility complex (MHC)-I and -II antigens, alpha and gamma interferon, and HIV antigens (p24, gp120, and gp41) was performed using specific antisera. In specimens from HIV-positive and seronegative patients, the predominant cell population was CD8+ cells and macrophages invading or surrounding healthy muscle fibers that expressed MHC-I antigen on their surface. The endomysial infiltrates in specimens from HIV-positive patients differed from those seen in specimens from the seronegative patients only by a significant reduction of the CD4+ cells (12.6 +/- 3.2% versus 21.1 +/- 4.2%). HIV antigens were seen in occasional interstitial mononuclear cells (but not in muscle fibers) in 6 of the 21 specimens from HIV-positive patients. Interferon was not localized. We conclude that the development of HIV-associated polymyositis does not appear to be related to direct infection of the muscle fibers by HIV but rather is due to a T-cell-mediated and MHC-I-restricted cytotoxic process, perhaps triggered by HIV. Because this immunopathological mechanism is common in both HIV-associated polymyositis and polymyositis alone, it is suggested that viruses may also be responsible in triggering polymyositis.
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PMID:Immunocytochemical and virological characteristics of HIV-associated inflammatory myopathies: similarities with seronegative polymyositis. 185 78

A case of Kaposi's sarcoma in a child with no serologic evidence of human immunodeficiency virus (HIV) infection is reported. A 7-year-old boy with Stage IV non-Hodgkin's lymphoma, after conventional chemotherapy, underwent autologous bone marrow transplantation (ABMT). Five months later he presented with supraclavicular mass and mediastinal enlargement. A bone marrow biopsy showed hypoplasia with no signs of the underlying disease, whereas the excised mass revealed a typical histologic pattern of Kaposi's sarcoma. The child is currently being treated with recombinant alpha-interferon (alpha-IFN) and regression of the disease has been achieved.
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PMID:Kaposi's sarcoma in a child after autologous bone marrow transplantation for non-Hodgkin's lymphoma. 187 88

We investigated whether elevated serum levels of beta 2-microglobulin and neopterin were related to the abnormal in vivo production of interferon described in patients with human immunodeficiency virus (HIV) infection, and whether these factors might add to measurements of CD4+ T cells in predicting survival and tumor regression in patients with Kaposi sarcoma associated with AIDS. beta 2-Microglobulin and neopterin levels were strongly correlated (r = 0.82), and were each significantly higher in patients with detectable serum interferon-alpha activity. Inverse correlations were observed between prognosis and levels of these serum products. Prediction by CD4+ T-cell count of tumor regression after treatment with interferon-alpha and zidovudine was improved by each of two factors: (a) the presence or absence of endogenous interferon-alpha activity, and (b) a combined variable reflecting relative levels of the interferon-inducible products, beta 2-microglobulin and neopterin. The level of beta 2-microglobulin was the single best predictor of survival. When beta 2-microglobulin was not considered, the endogenous interferon-alpha variable was the best predictor of survival, and the prediction was enhanced by addition of the combined variable, or the neopterin value alone. We conclude that serologic markers, which directly or indirectly reflect activation of the endogenous interferon system, may be valuable adjuncts to CD4+ T-cell counts in assessing prognosis and selecting and evaluating treatments for patients with Kaposi sarcoma and AIDS.
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PMID:Relationship and prognostic value of endogenous interferon-alpha, beta 2-microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS. 189 8

The reservoir of Mycobacterium avium complex (MAC) during human infection is the mononuclear phagocyte. In these studies, the ability of certain macrophage-active cytokines to affect MAC growth in human alveolar macrophages was evaluated. Neither recombinant interferon-gamma (2 x 10(2) to 10(3) U/well of 5 x 10(5) cells) nor recombinant macrophage colony-stimulating factor (20 to 50 ng/well), when tested alone, exhibited a consistent ability to induce macrophage targets to inhibit the growth of a clinical strain of MAC serovar 4. However, the combination of these cytokines (1 to 50 ng macrophage colony-stimulating factor + 10(3) U interferon per well) was remarkably effective in diminishing replication of MAC in all experiments. These cytokines were also able to induce alveolar macrophages to restrict MAC growth even though cells were obtained from several individuals with acquired immunodeficiency syndrome (AIDS) or from normal donors and infected in vitro with the human immunodeficiency virus type 1. The effect of this cytokine combination was not abrogated by 10(4) neutralizing U/ml of anti-tumor necrosis factor-alpha antibody. Rather, the combination of interferon-gamma and macrophage colony-stimulating factor appeared to activate intrinsic macrophage mechanisms for restricting MAC growth and deserves further study to determine the potential value of this cytokine combination in the treatment of human infection.
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PMID:Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma. 190 Apr 25

The host factors involved in the restriction of tumor growth were studied in nude mice transplanted with a cloned line of chronically human immunodeficiency virus (HIV)-infected U937 cells. HIV-infected and uninfected U937 cells exhibited the same growth patterns in culture. However, HIV-infected cells were not tumorigenic when injected subcutaneously in nude mice, whereas large solid tumors were observed in mice injected with uninfected U937 cells. Injection of nude mice with antibody to alpha/beta interferon (IFN-alpha/beta) enabled HIV-infected U937 cells to grow progressively in approximately 90 to 100% of mice. HIV-infected U937 cells formed solid tumors in the majority (60 to 90%) of either immunosuppressed (splenectomized, irradiated, and anti-asialo-GM1-treated) or genetically immunodeficient (bg/nu/xid) nude mice. In mice treated with antibodies to IFN-alpha/beta with established HIV-positive tumors, a direct correlation was found between p24 antigenemia and tumor size. Treatment of established HIV-positive U937 cell tumors with human IFN-alpha or mouse IFN-alpha/beta resulted in a clear-cut inhibition of both tumor growth and p24 HIV antigenemia. In contrast, treatment with tumor necrosis factor alpha markedly inhibited tumor growth but did not significantly decrease serum p24 levels. 3'-Azido-3'-deoxythymidine treatment did not affect either tumor growth or the levels of serum p24 antigen. These data indicate that endogenous IFN-alpha/beta is a crucial factor in the restriction of both tumor growth and p24 antigenemia in mice injected with HIV-infected tumor cells. Moreover, the results suggest that the development of HIV-1 p24 antigenemia in athymic immunosuppressed mice may represent an interesting in vivo model for anti-HIV therapy.
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PMID:Human immunodeficiency virus (HIV)-infected tumor xenografts as an in vivo model for antiviral therapy: role of alpha/beta interferon in restriction of tumor growth in nude mice injected with HIV-infected U937 tumor cells. 190 15


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