Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncostatin-M is a cytokine produced by macrophages and activated T lymphocytes that has recently been shown to be a mitogen for AIDS-related Kaposi's sarcoma (KS)-derived spindle cells. The significance of oncostatin-M production in AIDS-related KS in vivo, however, remains unknown. In this study we wanted to determine whether oncostatin-M is expressed in vivo in patients with HIV-I-related KS, define the cell types that express this cytokine, and compared with the control tissues from HIV-I-negative individuals. A second objective of our study was to define the expression of oncostatin-M in AIDS-KS-derived spindle cell isolates cultured in vitro and to determine whether oncostatin-M is an autocrine growth factor for these KS cells. We have determined that oncostatin-M is not expressed in any of the several organs examined in control cases, whereas the tumor tissue obtained from the skin biopsies of HIV-I-infected cases with KS displayed oncostatin-M expression in the spindle cell components of the tumor, as well as the cells lining the vascular structures, smooth muscle cells lining the eccrine sweat glands, and the epidermal layers of the skin. Furthermore, uninvolved skin of patients with HIV-related KS express oncostatin-M in the cells lining normal vessels. The mRNA polymerase chain reaction analysis confirmed findings in the primary tissues and showed expression in all of the AIDS-KS-derived spindle cell isolates examined. We have also shown with the use of oncostatin-M-specific antisense oligodeoxynucleotides that KS cell proliferation is inhibited, which correlated with a more precipitous decline in the production of interleukin-6 by these cells. We conclude that oncostatin-M is only expressed in the skin and KS tumor of HIV-I-infected individuals. Furthermore, we provide evidence that oncostatin-M is an autocrine growth factor for KS.
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PMID:Oncostatin-M is an autocrine growth factor in Kaposi's sarcoma. 803 Jul 59

The most virulent primate lentivirus identified to date, the simian virus SIVsmmPBj14 (SIV-PBj14), is unique not only because it causes acute disease and death within days instead of months or years, but also because of its replicative and cellular activation properties. The acute disease syndrome has many features in common with primary HIV-1 disease, but differences in the respective outcomes of these two acute lentiviral infections appear to be linked to the rapidity with which SIV-PBj14 replicates and the high titers of virus that subsequently accumulate in lymphoid tissues. The most prominent pathologic feature of SIV-PBj14 is extensive lymphoid hyperplasia of T-cell zones, especially in the gut-associated lymphoid tissue. These expanded T-cell zones contain a high proportion of lymphoblasts, activated macrophages and syncytial cells, which are positively correlated with high numbers of SIV antigen-positive cells. Replication of the virus to high titers, accompanied by extensive cellular activation and proliferation, leading to high levels of cytokines, such as interleukin-6 and tumor necrosis factor-alpha, are consistent with acute inflammatory disease. The pathogenesis of SIV-PBj14 also appears to correlate most directly with some of its unique biologic properties, such as the ability to replicate in resting peripheral blood mononuclear cells, to activate lymphocytes, and to induce lymphocyte proliferation. Biologically and molecularly cloned viruses derived from SIV-PBj14 and isolates obtained from macaque PBj at earlier times, are being used to identify viral determinants that influence biologic and pathogenic properties of SIV-PBj14. Further characterization of this virus should provide new insights into lentivirus-cell interactions and their contributions to disease.
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PMID:Unique lentivirus--host interactions: SIVsmmPBj14 infection of macaques. 806 54

The immune response of normal human peripheral blood mononuclear cells (PBMC) after stimulation with human immunodeficiency virus-1 (HIV-1) antigens plus Leishmania donovani promastigotes in vitro was investigated. HIV-1-antigen stimulation of PBMC did not induce the intracellular accumulation of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma). However, cells stimulated with L. donovani antigens exhibited the production of IL-6 and TNF-alpha, but not IFN-gamma. Furthermore, co-stimulation of PBMC with HIV-1 antigen plus L. donovani resulted in the intracellular accumulation of IL-6 and TNF-alpha comparable to that of cells that were activated with L. donovani antigen alone. Heat-inactivated HIV-1 antigen did not appear to induce or suppress cytokine production by PBMC. However, the same HIV antigens did suppress L. donovani-induced proliferation as well as PPD-induced proliferation in a dose-dependent fashion. Elevated levels of serum cytokines have been demonstrated in patients with HIV infection indicating their role in the pathogenesis of HIV-associated immunosuppression. The results may partially support the idea that the abnormally increased cytokine levels in the sera of HIV-infected subjects is due to the various opportunistic pathogens that these patients contract, rather than a response to HIV antigens. As cytokines have been shown to up-regulate HIV replication, the data suggest a role for opportunistic infections in cytokine-induced transactivation of HIV-1 and disease progression.
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PMID:HIV-1 inhibits Leishmania-induced cell proliferation but not production of interleukin-6 and tumour necrosis factor alpha. 814 97

Manifestations of HIV-1 infection such as fever, hypergammaglobulinemia, and interstitial pneumonitis may be due to increased production of inflammatory cytokines such as interleukin-1 and interleukin-6 (IL-6). Monocytes/macrophages of HIV-1-infected individuals have been noted to produce increased amounts of IL-6, as well as to have enhanced accessory cell function. These studies examined the ability of HIV-1 tat, an important HIV-1 regulatory gene, to modulate monocyte/macrophage function. In these experiments, HIV-1 tat-transfected THP-1 cells, a monocytic cell line, enhanced THP-1 immune accessory cell function in the presence of pokeweed mitogen and concanavalin A. HIV-1 tat-transfected cells also increased production of lipopolysaccharide-stimulated IL-6 mRNA and IL-6 protein. The ability of monocytes/macrophages to support HIV-1 production while exhibiting little or no cytopathic effects allows these cells to serve as a reservoir for the virus. The ability of HIV-1 tat to regulate cellular function in monocytes/macrophages may play an important part in the pathogenesis of HIV-1 infection.
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PMID:Modulation of accessory cell function and interleukin-6 production by the HIV-1 tat gene. 817 23

Kaposi's sarcoma was one of the first conditions defining the new disease AIDS in 1981. From the outset, it was quite apparent that the biology of Kaposi's sarcoma in the setting of AIDS was quite different from that of most other known neoplasms. This observation led many investigators to speculate that Kaposi's sarcoma is, in fact, a reactive tumor and not a true malignancy. Our understanding of the pathogenesis of Kaposi's sarcoma has evolved over the years, and it now believed that the tumor arises from mesenchymal cells, which are influenced by HIV, various cytokines or growth factors, and perhaps other viruses or environmental factors operating in the setting of immune suppression. The tumor itself has various clinical manifestations, ranging from indolent cutaneous tumors to rapidly growing tumors involving lung and other viscera. New approaches to the treatment of Kaposi's sarcoma include inhibition of angiogenic and Kaposi's sarcoma stimulating growth factors, eg, interleukin-6, fibroblast growth factor, tumor necrosis factor, oncostatin-M, and the HIV-tat gene product. Additionally, improvement in our use of cytotoxic chemotherapy, interferons, and antiretroviral drugs has led to better management of complications of the tumor and of HIV itself. This review highlights recent advances in our understanding of Kaposi's sarcoma and its treatment, with a focus on pathogenesis and novel therapies.
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PMID:Clinical aspects of AIDS-related Kaposi's sarcoma. 821 96

The level of human immunodeficiency virus type 1 (HIV-1) in lymphocytes and mononuclear phagocytes (MP) from the blood and pulmonary alveoli from 14 HIV-1-infected subjects during early (asymptomatic) and late (AIDS) stages of disease and the relationship between virus burden in MP and cytokine expression were assessed. Among asymptomatic subjects, HIV-1 was undetectable or low in both blood monocytes and alveolar macrophages (AM). Among subjects with AIDS, there was a significant increase of HIV-1 in AM but not monocytes. The level of HIV-1 in blood lymphocytes was higher than in either monocytes or AM. AM (but not monocytes) expressed increased levels of lipopolysaccharide-stimulated cytokine mRNA (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) during both early and late stages of HIV-1 infection regardless of virus load. AM thus may serve as a reservoir for virus in late stages of disease yet contribute to the immunopathogenesis of lung disease in both early and late stages through increased cytokine expression.
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PMID:Relationship between load of virus in alveolar macrophages from human immunodeficiency virus type 1-infected persons, production of cytokines, and clinical status. 827 80

The lectin jacalin is mitogenic for CD4 expressing T lymphocytes, interacts with the CD4 molecule, and inhibits HIV infection of CD4+ cells. In the present study the effect of jacalin was tested on cells from the monocyte/macrophage lineage that also express the CD4 molecule. We used CD4+ promyelomonocytic U937 cells differentiated towards the monocytic/macrophage lineage with either a mixture of two physiological agents, retinoic acid (RA) and 1 alpha,25-dihydroxyvitamin D3 (VD), or the exogenous drug phorbol myristate acetate (PMA). The cells resulting from these treatments differed in term of CD4 expression. We focused our attention on interleukin-6 (IL-6) production, which implies an activation of the cells differentiated along both pathways. In CD4+ RA/VD-treated cells, jacalin induced a 10-fold higher IL-6 secretion than did lipopolysaccharide (LPS). This jacalin-induced IL-6 production was inhibited by agents interacting with CD4 (anti-CD4 mAbs and HIV recombinant gp120) or by recombinant soluble CD4. In contrast, the CD4- PMA-differentiated U937 cells did not secrete any IL-6 upon jacalin treatment, while they demonstrated a response to LPS similar to that of the RA/VD-differentiated cells. Together with the fact that jacalin interacts with CD4, these results provide evidence of the involvement of a CD4 dependent pathway in IL-6 production.
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PMID:Involvement of CD4 in interleukin-6 secretion by U937 monocytic cells stimulated with the lectin jacalin. 830 Dec 19

The cytokine network, which is involved in the regulation of normal immune responses, may play a role in the pathogenesis of human immunodeficiency virus (HIV) infection, by altering the replication of HIV in target cells. In vitro data, suggest that certain cytokines like "tumor necrosis factor" alpha (TNF alpha) "granulocyte-macrophage colony-stimulating factor" (GM-CSF) and interleukin-6 (IL-6) could up-regulate HIV expression in T-cells and macrophages. Other cytokines like alpha interferon, are potent inhibitors of HIV replication. Surprisingly, the macrophage and the T-lymphocyte, the main source of cytokines in the body, do not produce any of these cytokines following HIV infection. B-lymphocytes however, spontaneously release TNF alpha and IL-6, that might enhance HIV replication in nearby monocytes and T-lymphocytes. This situation may occur in lymph nodes, a major reservoir of HIV.
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PMID:[Role of cytokines in the regulation of HIV expression]. 830 20

Azidothymidine (AZT) has been demonstrated to increase platelet counts in patients suffering from acquired immunodeficiency syndrome (AIDS). However, the ability of long-term AZT treatment to sustain increases in platelet counts is controversial. We have recently demonstrated that AZT elevates the levels of circulating platelets in both normal C57BL/6 mice and mice made immunodeficient by infection with LP-BM5 murine leukemia virus (MAIDS mice). We therefore studied the effect of long-term AZT administration on platelet formation in both normal and MAIDS mice. Peripheral blood indices, levels of femoral and splenic megakaryocyte colony forming units (CFU-MK), and plasma levels of cytokines important in platelet formation-interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF)--were examined. Platelet counts remained elevated throughout a 120-day AZT treatment period. Splenic CFU-MK were not significantly changed in MAIDS mice, except at day 15 when they were elevated. Splenic CFU-MK were significantly decreased in normal mice at days 8 and 120, and increased at day 30. Bone marrow CFU-MK were increased by AZT treatment at all time points tested in both normal and MAIDS mice. Plasma levels of GM-CSF were unchanged by AZT treatment in both normal and MAIDS mice. Plasma levels of IL-6 were unchanged in AZT-treated normal mice but decreased in AZT-treated MAIDS mice. These results indicate that long-term AZT treatment maintains elevated levels of platelets in both normal and MAIDS mice and affects CFU-MK colony formation. Our studies add to a growing body of work suggesting that AZT can ameliorate thrombocytopenia associated with HIV disease.
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PMID:Sustained elevation of platelet counts by long-term azidothymidine treatment of immunosuppressed mice. 845 34

In this study we evaluated the effect of recombinant interferon-alpha 2b (IFN-alpha 2b) therapy on the number of circulating platelets and interleukin-6 (IL-6) plasma levels in 12 human immunodeficiency virus type 1 (HIV-1) seropositive patients, affected by a severe and persistent thrombocytopenia. The levels of IL-6 in plasma of HIV-1 seropositive thrombocytopenic subjects before IFN-alpha therapy were similar (80 +/- 15 pg/ml) to those observed in 15 HIV-1 seropositive asymptomatic individuals (75 +/- 12 pg/ml) and 30 HIV-1 seronegative blood donors (59.5 +/- 25 pg/ml). On the other hand, IL-6 amounts (148 +/- 36 pg/ml) in plasma of HIV-1 seropositive thrombocytopenic subjects were significantly (p < 0.01) increased after 5 weeks of IFN-alpha 2b therapy, showing a good correlation (p < 0.05, chi-square test) with the levels of circulating platelets. Moreover, an increased spontaneous IL-6 production by peripheral blood monocytes was observed after IFN-alpha 2b therapy in HIV-1 seropositive thrombocytopenic patients. Our results suggest that an increased production of IL-6, one of the main factors controlling thrombocytopoiesis, may partially explain the ability of IFN-alpha 2b therapy, to restore platelet production in a subset of HIV-1 seropositive thrombocytopenic individuals.
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PMID:The elevation of circulating platelets after IFN-alpha therapy in HIV-1 seropositive thrombocytopenic patients correlates with increased plasma levels of IL-6. 846 69


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