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)

We examined the roles of interleukin-1 Type I receptor (IL-1R1) and tumor necrosis factor receptor 1 (TNFR1) in bone metabolism using mice rendered deficient in these receptors by gene targeting. Sections of decalcified paraffin-embedded calvariae and humeri from 11- to 12-week-old mice deficient in IL-1 Type I receptor (IL-1R1-/-) or TNF receptor 1 (TNFR1-/-) were examined by histomorphometry. Wild-type mice (C57BL/6J x 129/J, WILD) served as controls. Interleukin-6 (IL-6) production in primary osteoblastic and bone marrow stromal cell cultures in response to parathyroid hormone (PTH, 100 ng/ml), IL-1 alpha (10 ng/ml), and TNF-alpha (10 ng/ml) was also examined. IL-1R1-/- and TNFR1-/- mice were viable and appeared phenotypically normal. However, the body weights of the IL-1R1-/- mice were 30% less than WILD, while the TNFR1-/- mice weighed 30% more than WILD mice of equivalent age. Calvariae and humeri of IL-1R1-/- and TNFR1-/- mice were normal with respect to trabecular bone volume, osteoclast number, osteoclast surface, growth plate widths, and cortical thickness. Receptor deficiency was confirmed by determining the ability of PTH, IL-1 alpha, and TNF-alpha to stimulate IL-6 in the media of primary calvaria-derived osteoblastic cell cultures from CD-1 and cytokine receptor-deficient mice. After 24 h of treatment, IL-1 alpha and TNF-alpha did not stimulate IL-6 production in osteoblasts from IL-1R1-/- and TNFR1-/- mice, respectively. In contrast, PTH increased IL-6 levels in the cells from all mice. IL-6 protein levels in bone marrow supernatants and conditioned media from untreated bone marrow stromal cells were undetectable in WILD, IL-1R1-/-, and TNFR1-/- mice. PTH, IL-1 alpha and TNF-alpha increased IL-6 mRNA and protein production in the WILD bone marrow stromal cells. In contrast, PTH and TNF-alpha increased IL-6 mRNA and protein levels in IL-1R1-/- bone marrow stromal cells while IL-1 alpha had no effect. These findings demonstrate that normal bone development in mice can occur in the absence of IL-1R1 or TNFR1 expression.
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PMID:Interleukin-6 expression and histomorphometry of bones from mice deficient in receptors for interleukin-1 or tumor necrosis factor. 891 81

Allograft rejection is the main cause of corneal graft failure. T lymphocytes and macrophages have been implied to be involved in corneal rejection, but little is known about the molecular mechanism in this process. In this study, cytokine mRNA expression in the cornea was analysed during experimental corneal transplantation. The donor and acceptor corneas of two groups of rats were studied after receiving an allo- (PVG to AO rat) or autograft (AO rat). For controls, central buttons and peripheral corneal rings of the non-transplanted contralateral eyes were used. At different post-operative days (1, 3, 7, 12 and 19), the corneas were removed and subjected to mRNA isolation. All corneal samples underwent semi-quantitative reverse transcriptase-polymerase chain reaction analysis for interleukin-1 beta, interleukin-1, receptor antagonist, interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-alpha, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA expression. Corneal rejection, characterized by opaque corneas with prominent neovascularization, was always diagnosed around day 12. Contralateral, non-grafted corneas showed constitutive mRNA expression for interleukin-1 receptor antagonist and in a few samples also monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA was found. Both allo- and autografts expressed mRNA for the cytokines found in contralateral, non-grafted tissue, as well as for interleukin-1 beta, interleukin-6, interleukin-10 and tumor necrosis factor-alpha. In allografts, the mRNA levels for these cytokines remained constant throughout all post-operative days, with increased interleukin-6 mRNA expression after post-operative day 12. The analysis of the autografts revealed high cytokine mRNA levels until post-operative day 3 or 7, which decreased from then on, except for interleukin-1 receptor antagonist. mRNA for interleukin-2, interleukin-4 and interferon-gamma was not observed in autografts at any time point and in allografts, until post-operative day 12. Interleukin-2 and interferon-gamma mRNA showed maximal expression on POD 12, while in autografts, a marked decrease was observed after POD 3. IL-10 mRNA levels decreased immediately after POD 1 in autografted eyes. For TNF-alpha, an increased mRNA expression starting on POD 7 was found in recipient rings of allografted eyes, while in autografts a weak expression was seen in some samples. MIP-2 transcription increased on PAD 12, while in autografts, its expression was not markedly different from that detected in the contralateral, non-grafted peripheral cornea.
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PMID:Cytokine mRNA expression during experimental corneal allograft rejection. 894 52

In order to clarify the nature of T lymphocytes infiltrating the pancreatic islets of patients with insulin-dependent diabetes mellitus (IDDM), we analysed T cell receptor (TCR) gene transcripts expressed in pancreatic biopsy specimens of patients with recent-onset IDDM. We also investigated the expression of cytokines (interferon-gamma: IFN-gamma; tumour necrosis factor-alpha: TNF-alpha; interleukin-4: IL-4; interleukin-6: IL-6) in the same specimens. The TCR V beta repertoire was not restricted either in the pancreas or the peripheral lymphocytes of IDDM patients. In contrast, the TCR V alpha repertoire was restricted in the pancreas, but not in the peripheral blood lymphocytes, of IDDM patients. The sequence analysis of the complementarity-determining region 3 (CDR3) of the TCR alpha revealed the presence of dominant clonality in alpha chains of T cells in the patients. IFN-gamma mRNA was highly expressed in the pancreas of IDDM patients, while IL-4 mRNA was deficient. A lower level of expression of IL-6 mRNA was detected in the IDDM pancreas than in the control tissue. These results indicate that T cells bearing a distinct TCR alpha chain are selectively retained and activated within the pancreas of recent-onset IDDM.
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PMID:Dominant TCR alpha-chain clonotypes and interferon-gamma are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus. 896 89

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r = -0.54; P < 0.001; sTNF-R II: r = -0.47; P < 0.001) as well as interleukin-6 levels (r = -0.29; P < 0.01). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II (P < 0.01). The results of this study suggest that similar to its action in vitro, activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-alpha, this activation is particularly reflected by elevations of soluble TNF receptor levels.
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PMID:Inadequate erythropoietin response to anaemia in HIV patients: relationship to serum levels of tumour necrosis factor-alpha, interleukin-6 and their soluble receptors. 902 5

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.
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PMID:[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction]. 905 65

Bile acids have been proposed to exert immunological effects of potential pathogenic or therapeutic relevance, yet the experimental evidence remains preliminary. We reexamined the effects of a variety of bile salts with differing hydrophilic-hydrophobic properties on the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) from monocytes and Kupffer cells. Monocytes from healthy human donors and Kupffer cells from 5-week-old mice were incubated for up to 18 hours with or without varying concentrations of bile salts and lipopolysaccharide (LPS). Monocyte viability was > or = 95% with up to 250 mumol/L sodium ursodeoxycholate and < or = 90% with 200 mumol/L chenodeoxycholate, decreasing sharply at higher concentrations. Kupffer cells were more vulnerable, particularly to chenodeoxycholate (viabilities of 25% and 0% at concentrations of 100 mumol/L and 200 mumol/L, respectively). In monocytes incubated in the presence of 20% fetal calf serum, neither ursodeoxycholate and chenodeoxycholate, nor a variety of other unconjugated and conjugated bile acids, tested up to their maximal noncytotoxic concentrations, influenced the IL-6 and TNF alpha production, at any level of LPS stimulation. Similar to monocytes, incubation of murine Kupffer cells with ursodeoxycholate and chenodeoxycholate did not influence cytokine release. In contrast, the addition of 10 nmol/L dexamethasone to monocytes significantly decreased TNF-alpha and IL-6 release (69 +/- 11% and 48 +/- 15%, respectively). When monocytes were incubated with 200 mumol/L chenodeoxycholate in the presence of lower concentrations of fetal calf serum (10% and 5%, respectively) a significant inhibition of cytokine release was observed, whereas incubation with ursodeoxycholate did not cause any effect. Flow cytometry using fluoresceinated LPS showed that chenodeoxycholate does not interact with the CD14 receptor, thus excluding the possibility of an interference with the LPS uptake by monocytes. Incubation with [14C]-chenodeoxycholate showed that the intracellular bile acid uptake was inversely related to the concentration of fetal calf serum, being negligible (< 3 fmol/cell) at the highest level. In conclusion, bile acids with widely different hydrophobicities are incapable of influencing the release of IL-6 and TNF alpha by monocytes and Kupffer cells, provided they are studied at noncytotoxic concentrations and in the presence of physiological amounts of proteins.
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PMID:Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells. 909 99

Studies were undertaken to determine whether differences in serum cytokine balances could be involved in the pathogenesis of allergic and in non-allergic asthma. At this propose, interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, interleukin-6, and interleukin-10 were measured by enzimoimmunoassay. The analysis was performed on 24 allergic and 24 non-allergic asthmatic patients and 16 healthy subjects. IFN-gamma and TNF-alpha, included into the type 1 cytokines, appeared significantly increased in the allergic with respect to the non-allergic asthmatic patients (p = 0.01) and (p < 0.001) respectively, while IL-10, which belongs to the type 2 cytokines, was significantly increased in the non-allergic asthmatic (p < 0.001). The IL-6 analysis did not show any significant difference in either of the study group. The most interesting finding was the high serum IL-10 values detected in intrinsic asthmatic patients, which in turn, suggests that this cytokine could participate in the regulation of different immunological features that occurs in non-allergic asthma, and maybe it could indicate a higher stimulated state of cells in this type of asthma. The data presented in this report show a different cytokine profile in serum from allergic and non-allergic asthmatic patients and denote a stronger prevalence of type 2 cytokines in intrinsic asthma.
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PMID:Cytokine serum profiles in allergic and non-allergic asthma. Increased production of IL-10 by non-allergic asthmatic patients. 915 Aug 41

In response to antigenic stimuli, a variety of cells, including activated macrophages, secrete cytokines that are responsible for altering the host's metabolism. Three of these cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]) have profound behavioral, neuroendocrine, and metabolic effects. There is evidence that cytokines and their cognate receptors are present in the neuroendocrine system and brain. Moreover, in laboratory animal species, IL-1, IL-6, and TNF-alpha have been found to modulate intermediary metabolism of carbohydrate, fat, and protein substrates, regulate hypothalamic-pituitary outflow, and act in the brain to reduce food intake. Finally, many of the systemic acute-phase responses to inflammatory stimuli such as lipopolysaccharide are inhibited by treatment with cytokine receptor antagonists. In short, many findings converge to suggest that a major component of the growth inhibition observed in immunologically challenged animals is mediated by pro-inflammatory cytokines. The goal of this article is to provide an integrated view of how cytokines act systemically on disparate tissues to alter growth.
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PMID:Inhibition of growth by pro-inflammatory cytokines: an integrated view. 915 71

Tumor necrosis factor (TNF)-alpha is initially synthesized as an extracellular membrane-associated 26-kDa protein that is further cleaved at Ala76-Val77 to yield the soluble 17-kDa form. Recently, peptide-hydroxamate metalloproteinase inhibitors have been reported to block the proteolytic processing of TNF-alpha, thus suggesting that the putative TNF-alpha converting enzyme (TACE) is a zinc-dependent metalloendopeptidase. In this report, we characterize a TNF-alpha converting activity (TACA) that cleaves in vitro the human 26-kDa TNF-alpha at the physiological processing site. The chromatography steps followed for purification and the use of a panel of proteinase inhibitors indicate that the enzyme responsible for TACA is a membrane glycosylated metalloendopeptidase which is most likely different from the matrix-degrading metalloproteinases. The failure of TACA to process a Val77-->Gly77 precursor mutant emphasizes the importance of hydrophobic residue at P1' position. In addition, TACA is not able to cleave the mouse pro-TNF-alpha and does not catalyze in vitro the processing of other transmembrane proteins susceptible to metalloproteinase-mediated shedding, such as interleukin-6 or TNF receptors. These studies suggest the existence of an enzyme specific for TNF-alpha within the metalloproteinases involved in the processing/shedding of a number of cytokines and cytokine receptors.
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PMID:Partial purification and characterization of a tumor necrosis factor-alpha converting activity. 917 21

Our previous studies demonstrated that both in vivo and in vitro 3,4-dichloro-propionanilide (propanil) exposure inhibited interleukin-6 (IL-6) and tumor necrosis factor (TNF) production by adherent thioglycollate-elicited peritoneal cells (macrophages) after lipopolysaccharide (LPS) stimulation. In this study, we report that IL-6 and TNF-alpha message is reduced by propanil in a concentration-dependent pattern, yet the stability of cytokine mRNA is not affected. In addition, exposure of macrophages to propanil after a relatively short period of LPS stimulation significantly reduced the production of IL-6 and TNF. Determination of the intracellular Ca2+ levels demonstrates that LPS-induced Ca2+ release is abrogated in propanil-treated macrophages. However, the binding of LPS to macrophages is not affected. Measurement of inositol 1,4,5-triphosphate (IP3) demonstrates that propanil significantly increases the level and the duration of IP3 in macrophages. These results suggest that the inhibitory effect of propanil on macrophage cytokine production is associated with the early stages of LPS-mediated signal transduction in macrophages.
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PMID:Inhibitory effect of 3,4-dichloro-propionaniline on cytokine production by macrophages is associated with LPS-mediated signal transduction. 920 Dec 66


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