Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:009512 (tumor necrosis factor)
 58,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat. Transactivation of TNF gene expression requires the product of the first exon of the tat gene and is cell type independent. T cells chronically infected with pol-defective HIV-1 provirus constitutively express both Tat and TNF at levels significantly higher (fivefold) than those seen in control cells, and treatment with phorbol myristate acetate greatly enhances Tat expression and TNF production. As TNF can increase the production of IL-1 and IL-6 and these inflammatory cytokines all enhance HIV-1 gene expression and affect the immune, vascular, and central nervous systems, the activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses viral products and host factors to increase its own expression and infectivity and to induce disease.
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PMID:Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. 127 99

Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/microliters), who were treated concomitantly with recombinant human G-CSF (3-4 micrograms subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.
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PMID:Granulocyte colony-stimulating factor treatment in AIDS patients. 128 Apr 96

Monocyte/macrophage-mediated tumor cytotoxicity was studied in patients infected with human immunodeficiency virus-1 (HIV-1) at various stages [Center for disease control (CDC) classification] of the disease. using the P-815 tumor cell line as target cells, the results demonstrated reduced monocyte/macrophage cytotoxicity early in HIV-1-related disease (CDCIII, P < 0.01). This cellular dysfunction sustained during the progression of the disease. Evidence could be presented that neither exogenous application of macrophage-stimulating cytokines (e.g. interferons) nor their endogenous induction in vitro restored monocyte/macrophage cytotoxicity. However, enhanced tumor necrosis factor (TNF)-alpha production, which parallels the observed reduced capacity to lyse P-815 tumor cells, might be the major source for monocyte/macrophage-mediated cell lysis. TNF-alpha-induced cytotoxicity can be inhibited by addition of anti-TNF-alpha. Other experimental models using TNF-sensitive tumor target cells may, therefore, mimic monocyte/macrophage-mediated lysis. Suppression of monocyte/macrophage cytotoxicity in later stages of HIV-1 infection (AIDS-related complex, AIDS) could partly be reverted by treatment with the cyclooxygenase blocker, indomethacin. The responsible arachidonic acid product mediating suppression was found to be prostaglandin E2, suggesting that in addition to the direct viral interference cellular dysfunction is at least in part a result of altered cytokine regulation.
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PMID:Cytokine-mediated regulation of monocyte/macrophage cytotoxicity in human immunodeficiency virus-1 infection. 128 2

The paper presents examination findings of 67 HIV-infected patients: 32 children aged 2.5 to 16 years and 35 adults aged 21 to 46 years. The proportion of patients with higher alpha-tumor necrosis factor and interleukin-1 beta increased with progression of the disease, the two parameters being higher in the children than in the adults. A correlation was found between the appearance of cytokines in the plasma and some clinical signs, such as fever, weight loss, anemia, neurological disorders. A parallel study of the patients' immunograms indicated significant correlations between the degree of impairments in the composition of lymphocyte subpopulations and the appearance of plasma cytokines.
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PMID:[Tumor necrosis factor-alpha and interleukin-1beta in the blood plasma of patients with HIV infection]. 128 18

Human cytomegalovirus (HCMV) is a potential cofactor in HIV-1 infection. To investigate the mechanism whereby HCMV promotes HIV-1 replication, a PBMC coculture assay which measures HIV-1 p24 antigen release was used as an index of viral replication. HCMV-stimulated PBMC were capable of inducing HIV-1 replication in cocultures with acutely infected PBMC; however, this occurred only when the PBMC were from HCMV-seropositive donors (598 +/- 207 versus 27 +/- 10 pg/ml p24 antigen with PBMC from HCMV-seronegative donors on day 6 of coculture). Upon stimulation with HCMV, PBMC obtained exclusively from HCMV-seropositive donors released tumor necrosis factor (TNF)-alpha (270 +/- 79 pg/ml at 18 h of culture). Monoclonal antibodies to TNF-alpha blocked the activity of HCMV-stimulated PBMC in cocultures both with acutely HIV-1-infected PBMC and with the chronically infected promonocytic line U1. Also, treatment of HCMV-stimulated PBMC with pentoxifylline, an inhibitor of TNF-alpha mRNA, markedly reduced HIV-1 replication in cocultures both with acutely and chronically infected cells. These results indicate that TNF-alpha is a key mediator of HIV-1 replication induced by HCMV-stimulated PBMC and support the concept that this cytokine plays an important role in the pathogenesis of HIV-1 infection.
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PMID:Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-alpha-mediated mechanism. 131 Jun 98

Cytomegalovirus (CMV) is a major cause of inflammatory organ disease in immunosuppressed persons. To elucidate the mechanisms of CMV-induced inflammation, we investigated whether tumor necrosis factor-alpha (TNF-alpha) was involved in the pathogenesis of CMV colitis in patients with AIDS. In in situ hybridization experiments, TNF-alpha mRNA was shown to be abundantly present in colonic mucosa from AIDS patients with CMV colitis but not in colonic mucosa from control (AIDS and normal) subjects. The TNF-alpha transcripts, identified in macrophage-like cells containing cytomegalic inclusions, were positively associated with CMV, but not HIV-1, within the mucosa. In in vitro experiments, a patient-derived isolate of CMV, but not HIV-1Ba-L, induced human monocytes to express TNF-alpha mRNA and to release increased levels of TNF-alpha peptide following stimulation. CMV induction of TNF-alpha may play a critical role in CMV-induced inflammation and, since TNF-alpha upregulates expression of HIV-1, offers a mechanism by which CMV could serve as a co-factor for HIV-1 expression without both viruses infecting the same cell.
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PMID:Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. 133 Nov 70

Infection with the human immunodeficiency virus-1 is associated with a marked increase in the incidence of Kaposi's sarcoma. Recent studies suggest that the risk of Kaposi's sarcoma in human immunodeficiency virus infection is increased with oral-fecal contact and that a sexually transmitted agent possibly related to human papillomavirus-16 could be involved. Exposure to this or another sexually transmitted agent apparently alters both the morphology and growth regulation of the Kaposi's sarcoma progenitor cells. These changes include the expression of the alpha chain of the interleukin-6 receptor with the acquisition of an interleukin-6-dependent autocrine growth loop. Subsequent perturbation of multiple cytokines during human immunodeficiency virus infection, including Oncostatin-M, interleukin-1 beta and tumor necrosis factor-alpha alters the subsequent growth of Kaposi's sarcoma. These studies suggest that control of cytokine perturbations or the underlying human immunodeficiency virus-1 infection should result in a significant reduction in the rate of growth of acquired immunodeficiency syndrome-related Kaposi's sarcoma.
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PMID:Pathogenesis of human immunodeficiency virus-related Kaposi's sarcoma. 133 10

Disseminated toxoplasmosis, one of the most severe acquired immune deficiency syndrome (AIDS)-associated infections in humans, is believed to develop from a latent infection after the cellular immune system is suppressed by human immunodeficiency virus type 1 (HIV-1). However, Toxoplasma gondii may serve as a cofactor in enhancing the immunodeficiency induced by HIV-1. This hypothesis is supported by the facts that: 1) co-infection with other pathogens in humans infected with HIV-1 may enhance the progression of the disease to AIDS; and 2) concomitant infection with T. gondii enhances feline immunodeficiency virus-induced immune dysfunction and is likely to cause a more rapid disease onset than an infection with HIV alone. It is possible that T. gondii infection induces tumor necrosis factor (TNF) production. TNF then stimulates the induction of T-cell proteins that bind to the long terminal repeat of HIV-1. This binding at the repeat site then leads to increased HIV-1 activation which causes the dysfunction of CD4 cells and a resulting immunodeficiency that allows even greater amounts of T. gondii replication.
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PMID:Toxoplasma gondii: an AIDS enhancing cofactor. 133 11

Listeriosis is a not uncommon infection in humans, usually associated with immunodeficient states and with newborns. However, relatively few cases have been reported in HIV-infected patients. This scarcity of reported cases has aroused interest in the association of listeriosis and AIDS. In this paper we present a case of meningitis and septicemia caused by Listeria monocytogenes in a female patient with AIDS. A review of recent medical literature indicates that association of listeriosis and AIDS may be more common than it seems. Recent research in host-parasite interaction in listerial infection suggests an important role for tumor necrosis factor (TNF) and for integralin, a bacterial protein, in modulating listerial disease in AIDS patients. Inadequate diagnosis may be in part responsible for the scarcity of reports.
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PMID:Listeriosis and AIDS: case report and literature review. 134 13

We have analyzed the limiting factors involved in the induction of human immunodeficiency virus type 1 (HIV-1) provirus expression by tumor necrosis factor-alpha (TNF-alpha), phorbol-12-myristate-13-acetate (PMA), and bryostatin-1 in T-cells (ACH-2) and monocytes (U1). We have demonstrated that, while there is a correlation among the increase of 9.2-kilodalton (kDa) HIV-1 RNA, the increase of viral proteins (p24) in the cells, and the release of HIV-1 virions into the medium, there is no direct correlation between the levels of induced NF-kappa B binding proteins and the expression of HIV-1 provirus. The presence of nuclear NF-kappa B-specific proteins appears to be essential only for the initiation of viral replication, since the HIV-1 transcripts could be detected in TNF-alpha or bryostatin-1-stimulated cells also at later times postinduction, times when no NF-kappa B proteins could be detected in the nucleus. The uv crosslinking of DNA and proteins has shown that TNF-alpha, PMA, and bryostatin-1 induce different sets of NF-kappa B binding proteins with distinct kinetics of binding.
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PMID:Activation of human immunodeficiency virus type 1 provirus in T-cells and macrophages is associated with induction of inducer-specific NF-kappa B binding proteins. 137 Oct 30


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