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)

Human T-cell leukemia virus type I (HTLV-I)-infected T cells expanded in vitro by single-cell cloning provide a unique system for investigating virus-cell interactions in nonimmortalized T cells. By analysis of clones generated randomly from the blood of virus carriers, we confirm that CD4 T cells are the major reservoir of HTLV-I in vivo and show that most infected cells contain a single integrated provirus. Contrary to the situation in HTLV-I immortalized cell lines, the HTLV-I provirus was found to be transcriptionally silent in a high proportion of randomly generated T-cell clones and could not be reactivated by mitogenic stimulation. The spontaneous proliferation previously documented in HTLV-I-infected T-cell clones was not observed in silently infected cells, and therefore correlates directly with the expression of tax and other viral genes. The only cytokine mRNA found to be significantly elevated in the virus-producing clones was interleukin-6; however, receptor-blocking experiments argue against a role for IL-6 in the virus-induced cell proliferation. We observed a striking variation in the ability of individual HTLV-I-producing clones to immortalize fresh peripheral blood lymphocytes. This ability did not correlate with the levels of viral mRNA expression, gag p24 production, spontaneous proliferation, or tax-transactivation, possibly suggesting a role for host cell factors as determinants of viral infectivity or immortalization. Studies to elucidate the basis of this phenotypic heterogeneity should enhance our understanding of viral spread and pathogenesis.
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PMID:Variable immortalizing potential and frequent virus latency in blood-derived T-cell clones infected with human T-cell leukemia virus type I. 912 36

In a pilot study, seven patients with multiple sclerosis were treated with CAMPATH-IH which targets the CD52 antigen present on lymphocytes and monocytes. There was a substantial reduction in disease activity as measured by gadoliunium-enhancing lesions on MRI. Encouraged by this result a further seven patients have been treated with CAMPATH-IH; four also received anti-CD4 antibody. Lymphopaenia developed rapidly and was sustained for at least one year. In 12 patients, the first infusion of antibody was characterised by significant exacerbation or re-awakening of pre-existing symptoms lasting several hours. These clinical effects of antibody treatment correlated with increased levels of circulating cytokines. Peak levels of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) occurred at 2 h whereas the rise in interleukin-6 (IL-6) was significantly delayed and peaked at 4 h after starting antibody treatment. The neurological symptoms could not be attributed directly to pyrexia and were not provoked (in one patient) by an artificial rise in temperature. In the remaining two patients, a single pre-treatment with intravenous methylprednisolone (500 mg) prevented both the transient increase in neurological symptoms and the cytokine release. Our results suggest that soluble immune mediators contribute to symptom production in multiple sclerosis by directly or indirectly blocking conduction through partially demyelinated pathways.
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PMID:CAMPATH-IH in multiple sclerosis. 934 18

CD4 and CD8 T lymphocyte subsets, the late T cell activation marker, HLA-DR, and serum interleukin-6 (IL-6) levels of 57 polymyalgia rheumatica (PMR) patients were followed over 2 yr to investigate whether they could be used to predict the safe withdrawal of steroid therapy. Cell phenotypes were studied by flow cytometry and IL-6 levels by ELISA. %CD8 cells were reduced below the normal range in PMR patients prior to steroid therapy. In 56% of patients, the %CD8 T lymphocytes failed to return to normal levels when quiescent disease allowed cessation of steroid therapy. Activated CD8 T cells, as detected by HLA-DR positivity, were above the normal range at the initiation of therapy and showed a negative correlation with %CD8 T cells. The serum concentration of IL-6 fluctuated over 24 months, and the correlation between IL-6 and erythrocyte sedimentation rate (ESR) seen prior to treatment was not seen at later intervals. The %CD8 T cell and serum IL-6 levels are not a good indicator of disease activity in PMR and are, therefore, unable to predict the safe withdrawal of steroids.
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PMID:The sequential analysis of T lymphocyte subsets and interleukin-6 in polymyalgia rheumatica patients as predictors of disease remission and steroid withdrawal. 937 94

Interactions between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) mediate the earliest "rolling" of leukocytes on the lumenal surface of endothelial cells at sites of inflammation. Previously, PSGL-1 has been shown to be the primary mediator of interactions between neutrophils and P-selectin, but studies on the ability of PSGL-1 to mediate interactions between P-selectin and other subsets of leukocytes have yielded variable and conflicting results. A novel IgG monoclonal antibody (MoAb) to human PSGL-1 was generated, and the specificity of this MoAb was confirmed by both flow cytometric analysis and Western blotting of cells transfected with human PSGL-1. This newly developed MoAb, KPL1, inhibited interactions between P-selectin expressing COS cells and either HL60 cells, neutrophils, or lymphocytes. Furthermore, KPL1 completely inhibited interactions between P-selectin and either purified CD4 T cells or neutrophils in a flow assay under physiological conditions, but had no effect on interactions of T cells or neutrophils with E-selectin. In addition, KPL1 blocked interactions between lymphoid cells transfected with L-selectin and COS cells expressing PSGL-1. The KPL1 epitope was mapped to a site within a consensus tyrosine sulfation motif of PSGL-1, previously shown to be essential for interaction with P-selectin and now shown to be essential for interaction with L-selectin, and to be distinct from the epitope identified by the PL1 function blocking anti-PSGL-1 MoAb. Two-color flow cytometry of normal leukocytes showed that while natural killer (NK) cells (CD16(+)), monocytes, CD4 and CD8 T cells, and alpha/beta and gamma/delta T cells were uniformly positive for PSGL-1, B cells expressed low levels of the KPL1 epitope. This low level of KPL1 staining was also observed immunohistologically in germinal centers, which had no detectable KPL1 staining, whereas T-cell areas (interfollicular region) were positive for KPL1. Interestingly, plasma cells in situ and interleukin-6-dependent myeloma cell lines were KPL1(+). Thus, PSGL-1 is expressed on essentially all blood neutrophils, NK cells, B cells, T cells, and monocytes. Variation in tyrosine sulfation during B-cell differentiation may affect the ability of B cells to interact with P- and L-selectin.
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PMID:A novel P-selectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin. 941 80

gp130 is a common signal-transducing receptor component for the interleukin-6 (IL-6) family of cytokines. To investigate the expression of gp130 in T-cell subsets and its regulation, anti-murine gp130 monoclonal antibody (MoAb) was used for flow cytometric analysis. In normal mice, gp130 was differentially expressed in thymocyte and splenic T-cell subpopulations defined by CD4/CD8 expression. In aged MRL/lpr mice, although gp130 expression was detectable in splenic CD4(+) or CD8(+) T cells, gp130 expression was significantly downregulated. Because serum levels of IL-6 and soluble IL-6 receptor (sIL-6R) are elevated in these mice, we examined the possibility that the downregulation of gp130 expression on splenic T cells might be produced in response to continuous activation of gp130 by high levels of serum IL-6. In transgenic mice overexpressing IL-6, gp130 expression in the splenic T cells was significantly decreased. After stimulation with IL-6 in vitro, the level of gp130 on CD4(+) or CD8(+) splenic T cells from normal mice was significantly decreased. These results suggest that the expression of gp130 in splenic T cells could be downregulated by the IL-6 stimulation under physiological or pathological circumstances.
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PMID:gp130, the cytokine common signal-transducer of interleukin-6 cytokine family, is downregulated in T cells in vivo by interleukin-6. 955 87

The aim of this study was to evaluate the potential advantages of perioperative versus postoperative administration of an enteral immune-enhancing diet on host defense and protein metabolism. Thirty subjects, candidates for gastrectomy for cancer, were randomly allocated into two groups. The first group (n = 15) received an enteral formula enriched with arginine, omega-3 fatty acids, and RNA 7 d before and 7 d after surgery; the second group (n = 15) received the same diet but only 7 d after surgery. Postoperative immune and inflammatory responses were investigated by phagocytosis ability of polymorphonuclear cells, interleukin-2 receptors (IL-2R), lymphocyte subsets, interleukin-6 (IL-6), and delayed hypersensitivity response (DHR). Prealbumin (PA), retinol binding protein, albumin, and transferrin were determined as protein synthesis indicators. Perioperative immunonutrition prevented the early postoperative impairment of phagocytosis, DHR, total number of lymphocytes, and CD4/CD8 ratio (P < 0.05 versus postoperative group). The IL-2R levels were significantly higher in the perioperative group (P < 0.05 versus postoperative on postoperative day [POD] 4 and 8). Perioperative group also showed lower levels of IL-6 (P < 0.05 versus postoperative on POD 1, 4, and 8) and higher levels of PA (P = 0.04 versus postoperative on POD 8). The perioperative administration of immunonutrition ameliorated the host defense mechanisms, controlled the inflammatory response, and improved the synthesis of short half-life constitutive proteins.
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PMID:Immunonutrition in gastric cancer surgical patients. 983 29

Interleukin-6 (IL-6) is a multifunctional cytokine, with a wide range of effects on various cell types, including several types of cells involved in immune responses. IL-6 is believed to be involved in the pathogenesis of several diseases and may contribute to AIDS pathogenesis in various ways. Elevated levels of IL-6 occur in HIV infection. The objective of this study was to define the distribution of the expression of the 80-kDa alpha subunit of the IL-6 receptor (CD126'IL-6R') on immune cell subpopulations in HIV-infected subjects. CD126 is responsible for IL-6 binding, and its expression determines which cells respond to this cytokine. An elevated number of monocytes, B cells, and CD4 T cells expressing CD126 were seen in the peripheral circulation of HIV-infected subjects when compared to HIV-seronegative control subjects. Also, an increase in the density of CD126 expression was noted on monocytes. Generally, the observed increases in CD126 did not correlate with CD4 levels in HIV-infected subjects or with disease status, with the exception of CD126 expression on CD8 T cells, which was lower in those HIV-infected subjects that had AIDS. In some cases, increased CD126 expressing cells showed higher levels of STAT3 phosphorylation on exposure to recombinant IL-6. These results indicate that greatly elevated levels of CD126-expressing cells, particularly B cells and monocytes, are seen in HIV infection and suggest that the altered expression of CD126 may contribute directly or indirectly to immune dysfunction and to AIDS pathogenesis in HIV infection.
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PMID:IL-6 receptor (CD126'IL-6R') expression is increased on monocytes and B lymphocytes in HIV infection. 987 16

Vascular involvement in rheumatoid arthritis (RA) is associated with a wide range of extra-articular complications. Damage to internal organs occurs through a widespread disorder of the microvasculature. Vasculitis, as an integral part of the disease process, is associated with immune system abnormalities. To evaluate the relationship between capillaroscopic abnormalities, extra-articular involvement and immunological alterations, serum levels of soluble CD4 (sCD4), CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) were determined by an enzyme-linked immunosorbent assay in 80 RA patients. In all patients with signs of extra-articular manifestations, severe or moderate changes in nailfold capillaroscopy were found. Serum levels of TNF-alpha, IL-6, sIL-6R and sCD4 were significantly higher in RA patients compared with 30 healthy subjects. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of TNF-alpha and IL-6 compared with those without vascular involvement. Moreover, a significant correlation between sCD4 levels and the capillaroscopy findings was found. These results point to a pathogenic role of the cytokine network in rheumatoid vasculitis and further may suggest an important role of cellular immune activation in the pathogenesis of microvascular damage.
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PMID:Cytokines and soluble CD4 and CD8 molecules in rheumatoid arthritis: relationship to systematic vasculitis and microvascular capillaroscopic abnormalities. 989 Jun 77

In this study, we used a mouse model to examine the role of the adaptive immune response in alveolar bone loss induced by oral infection with the human gram-negative anaerobic bacterium Porphyromonas gingivalis. Severe combined immunodeficient mice, which lack B and T lymphocytes, exhibited considerably less bone loss than did immunocompetent mice after oral infection, suggesting that lymphocytes contribute to this process. Bone loss after oral infection was decreased in mice deficient in major histocompatibility complex (MHC) class II-responsive CD4(+) T cells, but no change in bone loss was observed in mice deficient in MHC class I-responsive CD8(+) T cells or NK1(+) T cells. Mice lacking the cytokine gamma interferon or interleukin-6 also demonstrated decreased bone loss. These results suggest that the adaptive immune response, and in particular CD4(+) T cells and the proinflammatory cytokines that they secrete, are important effectors of bone loss consequent to P. gingivalis oral infection. The studies also reinforce the utility of the mouse oral infection model in dissecting the pathobiology of periodontal disease.
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PMID:CD4(+) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. 1033 84

To investigate neuropathological processes involved in HIV infection, a longitudinal analysis of central nervous system (CNS) changes was performed using the SIV-infected macaque model. Five animals were studied during the early phase and 13 during the asymptomatic and symptomatic phases. Histopathological analyses were performed on one cerebral fixed hemisphere whereas on the other frozen hemisphere in situ hybridisation, immunohistochemistry and RT-PCR were performed. Viral load was quantified by in situ hybridisation, CD4 and CD8 T cell infiltration by immunohistochemistry and mRNA cytokine expression (IL1beta, IL2, IL6, TNFalpha, IFNgamma and TGF-beta1) by semiquantitative RT-PCR. As reported for HIV-infected humans, the neuropathological analysis of SIV infected animals revealed four distinct lesion profiles: minimal changes, early encephalitis, leukoencephalopathy and encephalitis. No relationship was found between neuropathological findings, numbers of SIV replicating cells and T cell infiltration. CNS infection was found to be an early event characterised by glial activation, an increase in the level of IL1beta, TNFalpha and IL6 mRNA expression. During the asymptomatic and symptomatic phases, IL6 and IL1beta mRNAs increase coincided with gliosis and the development of myelin lesions. The absence of relationship between neuropathological findings and viral load suggests that cerebral lesions are caused by an indirect mechanism. Inflammatory cytokine pattern associated with severe lesions show the key role of glial activation in the SIV neuropathological process.
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PMID:Viral load and neuropathology in the SIV model. 1041 13


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