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)

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.
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PMID:Macrophage colony stimulating factor involvement in uremic patients. 887 77

The consequences of complexing an antigen with specific antibodies upon the antigen-induced immune response were studied with respect to secretion of interleukin-2 (IL2), interleukin-6 (IL6), interleukin-10 (IL10) and interferon-gamma (IFN gamma). We found that the tetanus toxoid antigen-induced cytokine pattern was mainly dependent on the antigen/antibody ratio. While tetanus toxoid antigen alone induced a typical Th1-like cytokine pattern with high levels of IL2 and IFN gamma, equivalent or antibody-excess immune complexes induced a marked secretion of IL6 and IL10 while failing to induce IL2 and IFN gamma secretion. As the cytokine pattern plays a crucial role in the development of specific immune responses towards infectious agents, our results indicate that immune complexes--typically occurring during the course of chronic infectious diseases--may play an important role in the modulation of immune responses. Since a shift from Th1 to Th2 immune responses has been discussed as a pathogenetic factor in HIV-induced immunodeficiency, the role of circulating immune complexes as a possible cause for this shift should be considered.
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PMID:Distinct antigen-induced cytokine pattern upon stimulation with antibody-complexed antigen consistent with a Th1-->Th2-shift. 890 28

Interleukin-1 (IL-1) is elevated in brain tissue of individuals who died with acquired immunodeficiency syndrome (AIDS) and other diseases where this cytokine likely stimulates reactive astrocytosis. IL-1 stimulates, among others, production of interleukin-6 (IL-6), granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) in cultured astrocytes and astrocytoma cell lines. These and other cytokines may contribute to the neuropathogenesis after infection by human immunodeficiency virus type-1 (HIV-1). For example, concentration of TNF-alpha is increased in brain tissue of individuals who died with AIDS and correlates with the severity of AIDS Dementia Complex (ADC). TNF-alpha and IL-6 have been immunocytochemically detected in brain tissue but they have not been localized to astrocytes. We, therefore, examined the expression of IL-6, GM-CSF, and TNF-alpha in human primary astrocytes and astrocytoma cell lines U251 and 253 exposed to IL-1 in serum-free medium. In addition, we immunocytochemically assayed GM-CSF expression by astrocytes in brain tissue (n = 8). The three cytokines were differentially induced in cultured astrocytes by IL-1. The astrocytoma cell lines recapitulated cytokine-specific patterns of expression in astrocytes. The patterns were characterized by amounts produced, compartmentalization (intra- and/or extracellular), time courses, and optimal doses of IL-1 for induction. GM-SCF-like immunoreactivity was detected in some but not all, GFAP+ cells. GM-CSF+/GFAP+ cells were detected in only three of seven cases containing GM-CSF immunoreactivity. Thus, a discrepancy may exist between human astrocytic cytokine expression in vitro and in tissue. Novel methods therefore may need to be developed to recapitulate in vitro the heterogeneity of astrocytic cytokine expression in AIDS and other brain tissue.
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PMID:Distinct expressions of three cytokines by IL-1-stimulated astrocytes in vitro and in AIDS brain. 890 54

We describe a case of essential thrombocythemia observed in a 67-year-old woman with severe IgA-deficiency. The the best of our knowledge, this is the first report concerning the onset of a chronic myeloproliferative disease (CMPD) in a patient affected with primary immunodeficiency, in particular IgA-defect. The association may be merely coincidental; otherwise hemopoietic growth factors acting on myeloid progenitor cells could play a role in this relationship. It has recently been shown that serum levels of many cytokines are elevated in patients with CMPD and probably contribute to enhance proliferation of the malignant clones; on the other hand interleukin-6 seems to account for reactive thrombocytosis, and significant amounts of circulating interleukin-4 and interleukin-6 have been detected in IgA-deficient patients. Overproduction of the two cytokines may depend on recurrent infections, but it could also represent a primary abnormality, with a putative role in the pathogenesis of the immune defect. These findings suggest that high levels of growth factors could induce myeloid hyperproliferation and so expose stem cells to genetic mutations responsible for malignant transformation.
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PMID:[Primary thrombocythemia in a female carrier of IgA deficiency]. 902 53

Transfer of "anti-HIV-1 genes" into hematopoietic stem cells of human immunodeficiency virus-1 (HIV-1)-infected individuals may be a potent therapeutic approach to render mature cells arising from transduced stem cells resistant to the destructive events associated with HIV-1 infection. To determine the feasibility of gene therapy for acquired immunodeficiency syndrome in individuals already infected with HIV-1, granulocyte colony-stimulating factor mobilized peripheral blood CD34+ cells were isolated from HIV-1-infected individuals and transduced with retroviral vectors containing three different anti-HIV-1-genes: the Rev binding domain of the Rev Responsive Element (RRE decoy) (L-RRE-neo), a double hammerhead ribozyme vector targeted to cleave the tat and rev transcripts (L-TR/TAT-neo), and the trans-dominant mutant of rev (M10) (L-M10-SN). As a control, a vector mediating only neomycin resistance (LN) was used. After 3 days of transduction on allogeneic stroma in the presence of stem cell factor, interleukin-6 (IL-6), and IL-3, the cultures were G418-selected, and then challenged with HIV-1(JR-FL) and a primary HIV-1 isolate. Compared with the control cultures, the L-RRE-neo-, L-TR/TAT-neo-, and L-M10-SN-transduced cultures displayed up to 1,000-fold inhibition of HIV-1 replication after challenge with HIV-1(JR-FL) and the primary HIV-1 isolate. Growth of the hematopoietic cells in long-term bone marrow culture was not perturbed by the presence of any of the anti-HIV-1 genes. This study shows that anti-HIV-1 genes can be introduced into CD34+ cells from individuals already infected with HIV-1, and strongly inhibit HIV-1 replication in primary monocytes derived from the CD34+ progenitors.
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PMID:Inhibition of human immunodeficiency virus-1 (HIV-1) replication after transduction of granulocyte colony-stimulating factor-mobilized CD34+ cells from HIV-1-infected donors using retroviral vectors containing anti-HIV-1 genes. 911 67

Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1), as well as human T-cell leukemia-lymphoma virus type I (HTLV-I), may interact in the pathogenesis of human retroviral infections. The placental syncytiotrophoblast layer represents a barrier protecting the fetal compartment from exposure to retroviruses. We studied the interactions of EBV with HIV-1 and HTLV-I in human term syncytiotrophoblast cells to investigate the significance of double infections in transplacental transmission of human retroviruses. We found that syncytiotrophoblast cells could be productively infected with EBV. Dual infection of the cells with EBV and HTLV-I resulted in full replication cycle of otherwise latent HTLV-I. In contrast, the restricted permissiveness of syncytiotrophoblasts for HIV-1 was not influenced by coinfection of the cells with EBV. Infection of syncytiotrophoblast cells with EBV, but not HTLV-I, induced interleukin-2 and interleukin-6 secretion, and augmented secretion occurred on coinfection with both viruses. Coinfection of syncytiotrophoblast cells with EBV and HTLV-I induced tumor necrosis factor-beta and transforming growth factor-beta 1 secretion, but infection with either virus alone did not lead to secretion of these cytokines. Permissive replication cycle of HTLV-I was induced by the EBV immediate-early gene product Zta. Pseudotype formation between EBV and HTLV-I in coinfected syncytiotrophoblast cells was not found. Our data suggest that activation of HTLV-I gene expression by EBV in coinfected syncytiotrophoblast cells may be a mechanism for transplacental transmission of HTLV-I.
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PMID:Epstein-Barr virus permissively infects human syncytiotrophoblasts in vitro and induces replication of human T cell leukemia-lymphoma virus type I in dually infected cells. 912 52

Mice genetically deficient in the pleiotropic cytokine interleukin-6 (IL-6) exhibit immunodeficiency against viral, bacterial, and fungal pathogens. When challenged with the protozoan parasite Leishmania major, IL-6-deficient mice controlled infection and mounted strong Th1 responses as efficiently as IL-6-sufficient littermates. Thus, the successful activation of parasitized macrophages and class II-restricted T cells does not require a full inflammatory repertoire.
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PMID:Efficient immunity against Leishmania major in the absence of interleukin-6. 916 88

In order to ascertain if Cryptococcus neoformans components can induce interleukin-6 (IL-6) production, we stimulated human whole blood with purified capsular products. Their potencies in stimulating IL-6 release were mannoproteins > galactoxylomannan = glucuronoxylomannan > alpha(1-3)glucan. IL-6 production was tumor necrosis factor alpha independent and required the presence of monocytes and plasma. Since IL-6 can stimulate replication of the human immunodeficiency virus in monocytic cells, these findings may be clinically relevant.
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PMID:Interleukin-6 production by human monocytes stimulated with Cryptococcus neoformans components. 916 90

Human immunodeficiency virus (HIV)-related body cavity-based lymphomas (BCBLs) are known to exhibit unusual clinical, immunophenotypic, and genotypic features, and have recently been found to harbor DNA sequences of a new human herpesvirus, designated Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). The authors have encountered eight cases of HHV-8-associated BCBL in HIV-infected patients. A literature search revealed an additional 50 reported cases of HIV-related BCBL, as well as reports of several other disorders associated with HHV-8 DNA. Comprehensive analysis of the clinical and pathobiological features of all 58 known cases of HIV-related BCBL shows it to be a unique B-cell neoplasm with a strong propensity for body-cavity involvement without mass lesions and with little or no dissemination, poor prognosis, high grade usually immunoblastic morphology, late B-cell phenotype and genotype, no associated c-myc gene rearrangement, frequent presence of Epstein-Barr virus (EBV) genome, and uniform association with HHV-8 DNA. Considering these features in the context of other disorders associated with HHV-8 DNA, HHV-8 appears to play a causal role in BCBL, possibly in concert with EBV, and may induce this lymphoma through dysregulation of cytokines, particularly interleukin-6, or infection of an unusual B-cell subset. The characteristics of HHV-8-associated BCBL suggest a possible role for antiherpes or anticytokine agents in the treatment of this lymphoma.
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PMID:Human herpesvirus-8-associated body cavity-based lymphoma in human immunodeficiency virus-infected patients: a unique B-cell neoplasm. 922 48

The elderly are more prone to virus infections and neoplasias than are young adults. During a virus infection, interferon-alpha (IFN-alpha), proteins with antiviral, antiproliferative, and immunomodulatory properties, are transiently expressed. We here report that peripheral white blood cells from 16 subjects with a mean age of 72 years yielded less IFN when stimulated with a virus in vitro than those from 16 young adults with a mean age of 28 years. Monocytes are the main source of this IFN. However, yields of another monocyte product, interleukin-6 (IL-6), were greater in cells from the older subjects than from the young adults, so there is no general defect in monocytes from the former. Immunodeficiency in the elderly has been reported to be associated with a deficiency of zinc. When cultures of white blood cells from the elderly were supplemented with 15 microM zinc (the physiologic concentration), they produced IFN in amounts comparable to those from the younger subjects.
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PMID:Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons. 928 27


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