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)

Antibodies against lymphocytes have been shown in human immunodeficiency virus (HIV)-infected patients, but their relevance in the pathogenesis of acquired immune deficiency syndrome (AIDS) remains controversial. We investigated increased levels of lymphocyte surface Ig and antibodies against CD4+ T cells in the plasma. The relationship to CD4 cell depletion and serological parameters were analysed. A three-colour flow cytometric method was used to detect surface Ig on the surface of patients' cells and antibodies in the plasma of the patients. We observed a high percentage of patients with increased surface Ig on CD4+ T cells (94%-47/50). Antibodies in the plasma reacting with healthy donors' CD4+ T cells were detectable in 72% (23/32) of the patients. CD4 cell-surface Ig correlated well with surface Ig on different T-cell subpopulations but not with increased surface Ig on B cells. Only one control showed elevated surface Ig, plasma antibodies against lymphocytes were not detectable. Surface Ig levels of CD4+ T cells were closely associated with the CD4 cell number in HIV-infected patients of all stages of disease (r = -0.67, P = 0.00005). Other lymphocyte subsets' surface Ig did not show a significant association to CD4 cell depletion. Surface Ig and antibodies against CD4+ T cells were not related to levels of beta 2-microglobulin, p24 antibodies or interleukin-6 (IL-6), and did not depend on hypergammaglobulinaemia. In conclusion surface Ig on CD4+ T cells is likely to have an autoantibody origin. The high prevalence and association to CD4 depletion support the view that autoimmune phenomena could be involved in the pathogenesis of AIDS.
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PMID:Relationship of antibodies against CD4+ T cells in HIV-infected patients to markers of activation and progression: autoantibodies are closely associated with CD4 cell depletion. 810 20

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex organisms cause bacteremia in patients with AIDS. Human macrophages and murine Kupffer cells exposed to ethanol are more permissive towards intracellular growth of M. avium than control mononuclear phagocytes. Ethanol also has been shown to impair the ability of human macrophages and murine Kupffer cells to respond to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF), and to produce cytokines such as interleukin-1, interleukin-6, and TNF when properly stimulated. The impairment is dependent in part on a downregulation in the number of TNF receptors on the macrophage's membrane. Recent evidence suggests that ethanol in nonlethal concentrations induces stress-related proteins in M. avium, leading to the inhibition of intracellular pathways in the macrophage and, consequently, impairing some of its functions. In summary, ethanol acts both on the host and on the mycobacterium in a complex sequence of events that influence the outcome of the infection.
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PMID:Effect of ethanol on the interaction between the macrophage and Mycobacterium avium. 820 5

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 trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, syncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-alpha), transforming growth factors (TGF), platelet-alpha derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNF alpha, TGF beta, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte.
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PMID:The trophoblast as an integral component of a macrophage-cytokine network. 843 11

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

Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro. The diacylglycerol analogue phorbol myristate acetate (PMA) also induced MNGC. Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) failed to induce fusion. Preincubation of the IL-3 treated cultures with anti-IL-3, anti-leukocyte function associated antigen-1 (LFA-1) alpha-chain (CD11a), and anti-intercellular adhesion molecule-1 (ICAM-1) inhibited cell fusion. Antibody to polymorphic Class II major histocompatibility complex (MHC) determinants also inhibited MNGCs. Cell surface LFA-1 was predominantly observed on MNGC, suggesting that LFA-1 expression is involved in microglia fusion. We thus propose that MNGC formation of microglia result from the effects of T cell-derived cytokines probably through the induction of cell surface adhesion molecules.
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PMID:Lymphokine induction of rat microglia multinucleated giant cell formation. 850 64

Development of Kaposi's sarcoma (KS) after glucocorticoid therapy has been observed in a variety of clinical states including human immunodeficiency virus-1 infection and recent in vitro studies provided evidence for a direct stimulation effect of glucocorticoid hormones on KS cell proliferation. The importance of glucocorticoids in KS pathogenesis is further highlighted by the finding that glucocorticoids synergize with cytokines to promote acquired immune deficiency syndrome (AIDS)-associated KS (AIDS-KS) growth. Furthermore, cytokine effects were abrogated by the glucocorticoid antagonist RU-486. As glucocorticoid action is mediated through activation of their intracellular cognate receptors, we hypothesized that enhanced responsiveness of AIDS-KS cells to glucocorticoids may be due to elevated glucocorticoid receptor (GR) content. Indeed, high expression of GRs in AIDS-KS tumor biopsies was detected both at the level of mRNA and protein. Quantitative measurements of GRs in these specimens by a sensitive immunoassay showed that GR content was significantly elevated in the tumor tissue (4663 fmol/mg protein) compared with the uninvolved skin of the same patients (2777 fmol/mg protein), both of which were markedly above the normal skin of healthy donors (893 fmol/mg protein). Immunocytochemical analysis confirmed the presence of GRs in the cytoplasm and the nucleus of KS cells. Interestingly, four major KS cytokines, namely interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and oncostatin M, all of which are known autocrine growth factors for AIDS-KS cells, significantly increased the expression of functional GRs in cultured AIDS-KS cells. The latter result may explain, at least in part, the synergistic effect of glucocorticoid and oncostatin M on AIDS-KS cell proliferation. Thus, the high levels of GR expression in AIDS-KS and the up-regulation of GRs by KS-growth-promoting factors may confer enhanced and sustained sensitivity to the stimulatory effects of glucocorticoids. The data presented also provide molecular bases for therapeutic interventions targeting GRs in this disease.
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PMID:Expression and cytokine regulation of glucocorticoid receptors in Kaposi's sarcoma. 866 84

Central nervous system (CNS) involvement is common during human immunodeficiency virus type-1 (HIV-1) infection. The neurologic disease of the CNS most frequently observed during acquired immunodeficiency syndrome (AIDS) is HIV-1-associated cognitive/motor complex or AIDS dementia complex (ADC), which is most likely a direct consequence of HIV-1 infection of the CNS. The peripheral nervous system (PNS) is also affected in HIV-1-infected individuals and there are several features of immune- and cytokine-related pathogenesis in both the CNS and PNS that are reviewed. Several lines of evidence demonstrate aspects of immune activation in the CNS and peripheral nervous system (PNS) of HIV-1-infected individuals. The relative paucity of HIV-1 expression in contrast to widespread functional and pathologic changes in the CNS and PNS of AIDS patients, and the lack of evidence of productive infection of HIV-1 in neuronal cells in vivo lead to the possibility of indirect or immunopathogenic mechanisms for HIV-1-related neurologic diseases. Proposed mechanisms of neuronal and glial cell damage are injury of oligodendrocytes by tumor necrosis factor-alpha (TNF-alpha) released from activated macrophage/microglia, calcium-dependent excitoneurotoxicity induced by gp120 HIV-1 envelope protein, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity by quinolinic acid (a product of activated macrophages), cell injury by HIV-1-specific cytotoxic T cells, and apoptosis of oligodendrocytes or neurons triggered by interaction between cell surface receptors and HIV-1 gp120 protein. Common to those mechanisms is the dependence on cellular activation with expression of proinflammatory cytokines (TNF-alpha, interleukin-1). Amplification of activation signals through the cytokine network by macrophage/astrocyte/endothelial cell interactions, and cell-to-cell contact between activated macrophages and neural cells by upregulation of adhesion molecules dramatically enhances the toxic effect of macrophage products. Expression of immunosuppressive cytokines such as interleukin-4, interleukin-6, and transforming growth factor-beta is also increased in the CNS and PNS of HIV-1-infected patients. This may serve as neuroprotective and regenerative mechanism against insults to nervous system tissue.
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PMID:Role of immune activation and cytokine expression in HIV-1-associated neurologic diseases. 874 77

'Restricted' human immunodeficiency virus type (HIV-1) infection of astrocytes is recognized in vivo in some pediatric and adult AIDS brains and in vitro in a small proportion of transfected primary fetal astrocytes. We investigated the extent of HIV-1JR-FL expression in fetal astrocytes and macrophages cultivated alone or together. Peak HIV-1 p24 antigen titres in supernatant fluids of macrophage cultures were increased with monocyte/macrophages from certain donors and were higher when macrophages were cocultivated with astrocytes. Structural HIV-1 gene (gp 41 and pol) products (protein and mRNA) were observed only in macrophages. Ten days after HIV-1JR-FL infection, astrocytes in a monoculture were stained negative or only weakly positive (1-2+) for Nef, whereas in a coculture up to 100% of astrocytes displayed Nef staining (up to 4+) in the cytoplasm. The streptavidine-biotine-peroxidase technique with certain monoclonal antibodies to Nef (Ovod et al, 1992) was specific for infected astrocytes. The intensity of Nef staining was higher in astrocytes cultivated with monocyte/macrophages from certain donors. In the coculture, tumor necrosis factor-alpha (TNF-alpha) was expressed in the astrocyte cytoplasm earlier after coinfection with HIV-1 and cytomegalovirus (CMV) compared to infection with HIV-1 alone. Interleukin-6 (IL-6) was secreted spontaneously and transiently in uninfected cocultures, but in a prolonged fashion following HIV-1 and HIV-1/CMV infections. The interactions between HIV-1- and CMV-infected macrophages and astrocytes lead to upregulation of TNF-alpha and IL-6 and enhancement of productive HIV-1 infection of macrophages and of 'restricted' HIV-1 infection of astrocytes with implications for the pathogenesis of AIDS dementia.
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PMID:Regulation of HIV-1 infection in astrocytes: expression of Nef, TNF-alpha and IL-6 is enhanced in coculture of astrocytes with macrophages. 879 8


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