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)

Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN-beta were not detected nor was the mRNA expressed in either uninfected or HIV-infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV-infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes was coincident with high levels of 2',5' oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells. The markedly diminished capacity of HIV-infected monocytes to produce IFN-alpha may reflect a specific adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.
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PMID:A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. 198 24

The G0S19 genes are members of the "small inducible" family of genes, which have similar exon-intron organizations and encode secreted proteins with similar dispositions of cysteine and proline residues. G0S19-1 mRNA is increased shortly after the addition of lectin or cycloheximide to cultured human blood mononuclear cells. The cDNA sequence is homologous to that of a murine gene encoding an inhibitory cytokine (MIP1 alpha/SCI), which decreases hemopoietic stem cell proliferation. The homology extends to the 3' noncoding region, which contains two conserved elements: (i) GGGACTCTTC, a potential transcription factor NF chi B-binding site, and (ii) TTTTGTAATTTATTTT, which is found in some related genes (e.g., that encoding the immediate early protein ornithine decarboxylase). A similar but complementary sequence is present in human immunodeficiency virus. Two of the three human genes that hybridize to G0S19-1 cDNA were sequenced. G0S19-1 has 5' AP1-like recognition elements as found in some other phorbol ester-responsive genes (e.g., c-fos). G0S19-2 has a 5' Alu sequence, but is likely to be expressed because of the conservation of sections of the gene believed to be important for function. The 5' flanks of both genes contain the nucleotide motifs CK-2 and SRE, indicating cytokine-like genes with the potential to respond to growth factors. G0S19-1 is the main G0S19 gene expressed in adult T lymphocytes and may encode a homeostatic negative regulator of the size of cell populations (or subpopulations) which are derived ultimately from marrow stem cells. As such, it is a potential antioncogene.
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PMID:Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation. 227 Nov 20

Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-alpha-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-alpha mRNA and the secretion of TNF-alpha. Of note is the fact that anti-TNF-alpha antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-alpha antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-alpha, a cytokine involved in the complex network of regulation of the normal human immune response.
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PMID:Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. 230 May 61

The production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) by fresh peripheral blood mononuclear cells was evaluated after exposure to human immunodeficiency virus (HIV) or purified recombinant HIV-1 envelope glycoprotein (rgp120). To exclude the role of contaminating endotoxin in this study, all media were subjected to ultrafiltration and reagents contained less than 25 pg of endotoxin per ml by Limulus assay. Under endotoxin-free conditions, no increases in IL-1 beta, IL-6, or TNF-alpha mRNA or protein were detectable in cell cultures exposed to HIV-1, HIV-2, or rgp120 (0.1 to 10 micrograms/ml), as compared with cytokine levels in mock-exposed cultures. However, concentrations of endotoxin (lipopolysaccharide) as low as 0.5 ng/ml induced significant production of mRNA and protein for these three cytokines. Preincubation of mononuclear cells with "shake" HIV-1 preparations and also mock-infected shake preparations prior to lipopolysaccharide stimulation resulted in a two- to threefold increase in IL-1 beta and TNF-alpha production. This priming effect was not observed with rgp120 (0.1 to 10 micrograms/ml) or standard HIV-1 or mock-infected supernatants, suggesting the presence of biologically active material independent of virus in the shake preparations. Our studies indicate that, in the absence of endotoxin, HIV-1, HIV-2, and HIV gp120 do not induce production of IL-1 beta, IL-6, or TNF-alpha by peripheral blood mononuclear cells.
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PMID:Human immunodeficiency virus does not induce interleukin-1, interleukin-6, or tumor necrosis factor in mononuclear cells. 233 21

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) are potent immunomodulatory cytokines which are produced principally by cells of the macrophage-monocyte lineage. We conducted an investigation to assess the secretion of these cytokines by bronchoalveolar macrophages from patients with progressive stages of human immunodeficiency virus (HIV-1) infection. The mean level of TNF-alpha produced by macrophages from 9 patients with AIDS was significantly reduced compared with the responses of macrophages from 6 healthy HIV-1-seronegative persons, 6 patients with either asymptomatic HIV-1 infection or persistent generalized lymphadenopathy, and 6 patients with AIDS-related complex (ARC). The four study groups did not differ in their mean IL-1 beta responses. However, within the HIV-1-infected patient population, macrophages from 4 patients, 3 of whom had AIDS and 1 with ARC, failed to secrete detectable levels of IL-1 beta. All 4 patients were also nonresponsive in assays for TNF-alpha. These data establish that advanced HIV-1 infection may result in a pronounced dysfunction in the cytokine responses of alveolar macrophages.
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PMID:Production of tumor necrosis factor-alpha and interleukin-1 by alveolar macrophages from HIV-1-infected persons. 234 Feb 4

Binding of peptide hormones to surface membrane receptors leads to the transcription of specific genes within relevant target cells. How these signals are transduced to alter gene expression is largely unknown, but this mechanism probably involves a sequence of enzymatic steps that activate factors in the nucleus that modulate transcription. We now demonstrate that two different peptide hormones, or cytokines, stimulate the human immunodeficiency virus enhancer, and this effect is mediated by nuclear factor (NF) kappa B (nuclear factor that binds the kappa immunoglobulin light chain gene enhancer). These cytokines, tumor necrosis factor alpha and interleukin 1, act on multiple cell types and represent the only naturally occurring activators of this transcription factor among eight cytokines examined. Although NF-kappa B binding can be stimulated by phorbol 12-myristate 13-acetate, tumor necrosis factor alpha acts through an independent mechanism, inducing NF-kappa B binding in HT-2 cells, which did not show increased binding in response to phorbol 12-myristate 13-acetate, and causing superinduction in Jurkat T-lymphoma cells. Tumor necrosis factor alpha is also a more selective activator of T cells than phorbol 12-myristate 13-acetate, having no effect on lymphokine production in EL-4 cells at the same time it induces NF-kappa B. These findings suggest that human immunodeficiency virus gene expression can be induced in T cells without activating lymphokine secretion and that the role of these cytokines in the activation of latent human immunodeficiency virus infection deserves further clinical evaluation. Finally, this link between binding at the surface membrane and stimulation of a specific transcription factor should help define intermediates for these cytokine activation pathways.
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PMID:Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. 249 64

Bovine leukemia virus (BLV) infection of rabbits provides a safe and relatively inexpensive in vivo mammalian system for the study of the mechanisms controlling expression of a unique group of lymphotropic retroviruses. This group of viruses, which includes C-type human T-lymphotropic virus types I and II and lentiviruslike human immunodeficiency virus type 1, possesses genes coding for "trans-activating" products. Rabbits experimentally inoculated with BLV became persistently infected, as demonstrated by a number of tests. All BLV-inoculated rabbits developed persistent serum antibody to BLV. Furthermore, all BLV-inoculated rabbits had peripheral blood mononuclear cells which, when stimulated, expressed the virus, as demonstrated by viral induction of syncytium formation in a BLV-susceptible fibroblast line. The presence of BLV in circulating cells was confirmed by using peripheral blood mononuclear cells from randomly selected BLV-inoculated rabbits, which showed the presence of viral reverse transcriptase activity, BLV transcriptional activity, or BLV proviral DNA. Additional tests showed that infected lymphocytes maintained in culture with recombinant human interleukin-2 formed multinucleated giant cells and produced virus when incubated in cytokine-containing medium. BLV-infected rabbits also showed alterations in several parameters associated with immunity, beginning 6 months after inoculation. Thirty-eight percent of infected rabbits developed abnormally low T-cell responses, as measured by phytolectin stimulation, and T-cell responses cycled between normal and abnormally low over a period of 20 to 24 months. Forty-four percent of rabbits infected for longer than 12 months suffered from recurrent conjunctivitis and rhinitis. By 24 months postinoculation, 28% of infected rabbits were dead or were killed because of poor clinical condition.
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PMID:Persistent infection of rabbits with bovine leukemia virus associated with development of immune dysfunction. 255 35

Mononuclear phagocytes, including alveolar macrophages (AM), can be infected by the human immunodeficiency virus (HIV). Acting as accessory cells (AC), AM could infect CD4 lymphocytes through cell-to-cell contact and by inducing T cell proliferation, which increases lymphocyte susceptibility to infection. Using normal allogeneic T cells as responders, AM from infected individuals demonstrated an enhanced ability to stimulate a Con A and pokeweed mitogen lymphocyte proliferation assay compared with normal AM. Exogenous IL 1 enhanced the stimulation of a mitogen response by normal AM, but not from HIV-positive individuals, suggesting increased levels of this cytokine may explain the observed enhancement. However, increased IL 1 secretion by AM from HIV-infected patients could not be demonstrated, either in a bioassay or antigenically using an ELISA for IL-1 beta. Syncytia formation was observed when AM from asymptomatic HIV-positive individuals were cultured with normal T cells, suggesting viral transmission was occurring. Finally, in individual patients the stimulation of a mitogen response was inversely correlated with the CD4/CD8 ratio and total CD4 count, suggesting that enhanced AC function and CD4 cell depletion may be related in vivo. These findings indicate that enhanced AM accessory cell function is seen in HIV-infected individuals and could be a potential mechanism for CD4 cell depletion in the lung.
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PMID:Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung. 257 9

The human immunodeficiency virus (HIV) is the newly recognized agent of the acquired immunodeficiency syndrome (AIDS). Global defects of the immune functions, including T- and B-cell immunity, macrophage functions and cytokine production, are commonly observed among patients with HIV infection. Many studies have shown thymus involvement and endocrine function impairments among these patients. Clinical trials with thymic compounds aiming at restoring the immune dysfunctions will be reviewed.
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PMID:Preliminary results on clinical and immunological effects of thymus hormone preparations in AIDS. 265 50

The concept of the epidermis being a site for the initiation of immune responses has only been developed over the past decade. There is strong evidence that epidermal cells have immune functions. Accordingly the epidermis harbors dendritic cells having antigen presenting capacity and cells belonging to the T-cell family. Moreover, keratinocytes are capable of secreting various immunomodulating cytokines or secretory regulins. Cytokines are glycoproteins which are synthesized and secreted by various cells, bind to specific receptors and regulate activation, proliferation and differentiation of immune as well as non-immune cells. Keratinocytes upon injury i.e. mechanical irritation, ultraviolet irradiation, tumor promotors, synthesize and release interleukin-1 alpha, -1 beta, -6, -8, colony stimulating factors, tumor necrosis factors-alpha as well as growth (transforming growth factor beta) and suppressor (epidermal cell-contra-interleukin-1) factors. Since there is strong evidence in support of a network of interacting cytokines maintaining a proper balance which only partially has been discovered, so far no causative role of a single cytokine has been established in any disease. However, excessive or insufficient production of these mediators may contribute to certain disease states, particularly those of infectious and autoimmune origins. Thus, cytokines appear to be promising candidates for the treatment of infectious, autoimmune, immunodeficiency and malignant diseases. Future studies are necessary to clarify the therapeutic efficacy of the combined application of different cytokines and more investigations are also needed to elucidate the lymphokine cascade in vivo.
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PMID:Epidermal cytokines. 269 9


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