UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the changes in cellular components and cytokine levels (tumor necrosis factor, interleukin-6 and IL-8) before and after intrapleural tetracycline (TC) injection, we evaluated 10 patients with malignant pleural effusion. Differential cell counts in the pleural fluid were obtained using cytocentrifuge preparations. Mononuclear cells from pleural fluid, collected before intrapleural injection of TC, on Day 4, and Days 10 to 14 after TC injection, were stimulated either with phytohemagglutinin (PHA) or PHA plus phorbol myristic acetate. The production of tumor necrosis factor (TNF) and IL-8 was measured. In addition, IL-6, IL-8, and TNF from serial collections of pleural fluid in these patients were measured by RIA or ELISA. The main inflammatory cells in pleural effusions before therapy were lymphocytes and mononuclear cells, but neutrophils predominated after TC injection. IL-6, IL-8, and TNF were markedly increased on Day 4 after TC intrapleural injection and then decreased to baseline levels on Day 14. The results suggest that TC intrapleural injection induces the release of cytokines (IL-6 and TNF), which are markers of an inflammatory response, and releases IL-8, which attracts neutrophils into the pleural space, which may be the mechanism of the sclerosing effect of TC.
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PMID:Changes in cell population and tumor necrosis factor, interleukin-6, and interleukin-8 in malignant pleural effusions after treatment with intrapleural tetracycline. 850 62

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

The aim of our study (clinical phase II open pilot study) was to evaluate the toxicity of megestrol acetate and its ability to increase appetite and body weight in patients with advanced-stage (III-IV) primary head and neck squamous cell carcinoma treated with neoadjuvant (primary) chemotherapy. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha, and the soluble receptor for interleukin-2 were evaluated before and after megestrol acetate treatment. The same cytokines and soluble interleukin-2 receptor were also measured in culture medium of peripheral blood lymphocytes from the same patients after stimulation with phytohemagglutinin. From April 1993 to February 1994, 11 male patients were enrolled in our study: their mean age was 57.8 years (range 43-69 years). Megestrol acetate was administered at a dose of 320 mg/day in the interval between chemotherapeutic cycles for a total of three consecutive cycles; 9 of the 11 patients could be evaluated (81.8%). Except for the performance status according to Karnofsky, all parameters were increased after megestrol acetate treatment. The average weight increased by 6.3 kg (13.2%), appetite by a score of 2.4 (38.6%) and the Spitzer's quality of life index by a score of 2.4 (36.2%). The performance status according to Karnofsky decreased in only 1 patient, remained the same in most patients, and in 2 patients was slightly improved. No significant side effects were observed during treatment. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha, and soluble interleukin-2 receptor were significantly higher than in normal subjects, prior to treatment with megestrol acetate. These levels dropped after megestrol acetate treatment with a statistically significant decrease for interleukin-1 alpha and beta and tumor necrosis factor-alpha. There were no significant differences in the production of cytokines by peripheral blood lymphocytes stimulated with phytohemagglutinin from patients before megestrol acetate treatment and normal subjects, with the exception of interleukin-6 (higher in patients) and of soluble interleukin-2 receptor (lower in patients). There was no significant difference in the cytokines and soluble interleukin-2 receptor produced in culture before and after megestrol acetate treatment, except for interleukin-6 which decreased after treatment.
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PMID:Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and comparison with cytokine levels in patients with head and neck carcinoma treated with neoadjuvant chemotherapy. 856 75

Since mast cells and basophils are thought to play a central role in several types of cutaneous inflammatory and allergic reactions, and since interleukin-6 (IL-6) is an important mediator in these processes, we have studied the ability of the human mast cell line HMC-1, the human basophilic cell line KU812, and human skin mast cells to produce IL-6. All three cell types proved to be potent sources of this cytokine after appropriate stimulation. Transcription of IL-6 mRNA was first detectable 2 h after stimulation with the ester phorbol myristate acetate (PMA) and the calcium ionophore A23187 in both cell lines, as evidenced by semiquantitative reverse transcriptase polymerase chain reaction analysis. Whereas resting cells did not produce IL-6 protein, PMA/A23187-stimulated cells released immunoreactive and biologically active IL-6, as demonstrated and quantitated by enzyme-linked immunosorbent assay and by the use of TEPC 1033 cells, an IL-6-dependent murine plasmacytoma cell line. Stimulated KU812 cells secreted sevenfold more IL-6 (up to 15 ng/ml) than HMC-1 cells (up to 2.4 ng/ml). Immunoblotting of HMC-1- and KU812 cell-derived IL-6 revealed several IL-6 forms in the molecular weight range of 21 to 30 kDa. Immunoelectron microscopic studies of human skin biopsies provided evidence that unstimulated mast cells do not contain preformed IL-6 but accumulate IL-6 in cytoplasmic and extruded granules after IgE-dependent stimulation. These findings suggest that IL-6 secreted by human mast cells and basophils potentially contributes to allergic, other immunologically mediated and nonspecific inflammatory responses.
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PMID:Production of interleukin-6 by human mast cells and basophilic cells. 859 85

Recombinant human tumor necrosis factor (TNF) binding protein-1 (r-h TBP-1) and recombinant human soluble dimeric TNF receptor (rhu TNFR:Fc) were used to determine the relative contributions of TNF to phorbol myristate acetate (PMA) and cytokine-induced human immunodeficiency virus type 1 (HIV-1) replication in chronically infected cell lines. Treatment of HIV-1-infected promonocytic U1 cells with r-h-TBP-1 or rhu TNFR:Fc reduced PMA-induced HIV-1 p24 antigen production in a concentration-dependent manner, with a maximal inhibition of approximately 90%. Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47% with r-hTBP-1 and 42% with rhu TNFR:Fc. r-hTBP-1 and rhu TNFR:Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli, including phytohemagglutinin (PHA)-induced supernatant, granulocyte-macrophage colony-stimulating factor, interleukin-6, and TNF. Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15%. U1 cells stimulated with 10(-7) M PMA released approximately 1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation. r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA. Both r-hTBP-1 and rhu TNFR:Fc blocked PMA induction of nuclear factor (NK)- kappa B DNA-binding activity in U1 cells in association with decreases in HIV-1 replication. We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NK- kappa B DNA-binding activity in chronically infected U1 cells.
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PMID:Soluble tumor necrosis factor receptors inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically infected U1 cells. 860 87

Aging has been associated with diminished lung function and increased susceptibility to lung infection. To determine whether changes suggestive of immune dysregulation and inflammation appear in the lungs of clinically normal individuals as a function of advancing age, we performed bronchoalveolar lavage (BAL) on discontinuous age groups (20-36, 45-55, and 65-78 yr old) of clinically normal volunteer subjects. We measured immunoglobulin (IgG, IgA, IgM), albumin, interleukin-6 (IL-6), and interleukin-10 concentrations in BAL fluid. Bronchoalveolar cell profiles, cell surface antigen expression, and superoxide anion production were also measured. A significant increase in total cell concentration, neutrophils, and BAL immunoglobulin content was observed in the oldest age group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in blood (2.6 +/- 0.4 versus 1.6 +/- 0.1; p<0.03) and to a greater degree in BAL (4.8 +/- 1.0 versus 1.9 +/- 0.2; p<0.01) for the oldest versus youngest age groups. Similarly, BAL-derived cells displayed significantly increased phorbol myristate acetate-stimulated release of superoxide anion (8.8 +/- 1.3 versus 4.5 +/- 0.7 nmol/5 x 10 5 cells/h; p<0.01) for the oldest versus youngest subject group, and mean BAL IL-6 concentrations were significantly elevated in the oldest age group (0.86 +/- 0.13 ng/ml) compared with the youngest age group (0.53 +/- 0.03 ng/ml; p<0.01). Our observations suggest that altered inflammatory cell profiles and low-grade inflammation exist in the lower respiratory tracts of many asymptomatic, clinically normal volunteers of advanced age.
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PMID:Immune dysregulation in the aging human lung. 863 May 47

To investigate the role of the retinoblastoma protein pRB in neuronal differentiation, we have measured the accumulation of hypophosphorylated pRB in PC12 cells stimulated by nerve growth factor (NGF). NGF induced the accumulation of hypophosphorylated pRB within 30 min and the level peaked after 12 h. Viral Kiras, cyclic AMP (cAMP), and 12-O-tetradecanoylphorbol 13-acetate (TPA) also induced the hypophosphorylation of pRB, but epidermal growth factor and interleukin-6 did not. The extent of hypophosphorylation of pRB correlated well with the capacity of these factors to stimulate neurite outgrowth. The constitutively activated Ras induced persistent shift of the phosphorylation state of pRB toward hypophosphorylation. A dominant negative form of cHa-Ras suppressed significantly induction of the hypophosphorylation of pRB by NGF, but not by cAMP. Taken together, these results suggest that the hypophosphorylation of pRB triggered by NGF is mediated by a Ras-dependent pathway. Furthermore, microinjection of a monoclonal antibody specific for the hypophosphorylated form of pRB blocked the neurite outgrowth initiated by NGF. These results suggest a crucial role of pRB in withdrawal of cells from the cell cycle and in neuronal differentiation of PC12 cells.
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PMID:Ras-regulated hypophosphorylation of the retinoblastoma protein mediates neuronal differentiation in PC12 cells. 863 50

Activation of glial cells and the consequent release of cytokines, proteins, and other intercellular signaling molecules is a well-recognized phenomenon in brain injury and neurodegenerative disease. We and others have previously described an inducible prostaglandin G/H synthase, known as PGHS-2 or cyclooxygenase-2, that is up-regulated in many cell systems by cytokines and growth factors and down-regulated by glucocorticoid hormones. In cultured mouse astrocytes we observed increased production of prostaglandin E2 (PGE2) after stimulation with either interleukin-1 beta (IL-1 beta) or the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). This increase in PGE2 content was blocked by pretreatment with dexamethasone and correlated with increases in cyclooxygenase activity measured at 4 h. Northern blots revealed concomitant increases in PGHS-2 mRNA levels that peaked at 2 h and were dependent on the dosage of IL-1 beta. Dexamethasone inhibited this induction of PGHS-2 mRNA by IL-1 beta. TPA, basic fibroblast growth factor, and the proinflammatory factors tumor necrosis factor alpha and lipopolysaccharide, but not interleukin-6, also stimulated PGHS-2 mRNA expression. Relative to IL-1 beta, the greater increases in PGE2 production and cyclooxygenase activity caused by TPA correlated with a greater induction of PGHS-2 mRNA. Furthermore NS-398, a specific inhibitor of cyclooxygenase-2, blocked > 80% of the cyclooxygenase activity in TPA-treated astrocytes. These findings indicate that increased expression of PGHS-2 contributes to prostaglandin production in cultured astrocytes exposed to cytokines and other factors.
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PMID:Interleukin-1 beta induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary murine astrocyte cultures. 863 79

Titanium-aluminum-vanadium wear particles isolated from the soft-issue membrane of a failed total hip arthroplasty were added to human fibroblasts in cell culture. The cellular response to particle challenge was determined by assaying for levels of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, prostaglandin E2, basic fibroblast growth factor, platelet-derived growth factor-AB, and transforming growth factor-beta. Collagenase and gelatinase activities were analyzed by zymography and [3H]collagen degradation. Cell viability was assessed by measuring the uptake of [3H]thymidine. Over the range of particle concentrations tested, cell viability, as demonstrated by [3H]thymidine uptake, remained unaffected. Fibroblasts exhibited a dose-dependent release of interleukin-6 in response to exposure to titanium-aluminum-vanadium particles. At 6 and 48 hours, the highest concentration of titanium alloy particles (0.189% [vol/vol]) resulted in 7-fold and 16-fold increases in interleukin-6 release, respectively, when compared with negative controls. Neither interleukin-1 beta nor tumor necrosis factor-alpha was detected in the culture medium at any particle concentration tested for both dermal and foreskin fibroblasts. The pattern of prostaglandin E2 release by fibroblasts mirrored the pattern of interleukin-6 release. Fibroblasts exposed to the highest concentration of titanium alloy particles showed an increase in collagenase activity, starting at 12 hours. When medium samples were treated with amino phenylmercuric acetate to activate latent enzymes, a statistically significant increase in collagenase activity was observed as early as 6 hours (p < 0.001). Substrate gel analysis of medium from fibroblasts stimulated by high particle concentrations also showed an increase in gelatinolytic activity when compared with unstimulated controls. Analysis of medium samples for growth factors showed an increase in basic fibroblast growth factor at low particle concentrations, beginning at 12 hours. Levels of platelet-derived growth factor-AB and transforming growth factor-beta were not detectable in the controls or at any particle concentration tested. The results of this study showed that fibroblasts exposed to titanium alloy wear particles become activated and release proinflammatory mediators that influence bone metabolism. These data support the hypothesis that direct activation of fibroblasts by particulate wear may play a role in particle-mediated osteolysis. Fibroblast activation coupled with the biologic response of macrophages to wear debris in the loosening membrane may have a synergistic effect on pathologic bone resorption.
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PMID:In vitro activation of human fibroblasts by retrieved titanium alloy wear debris. 867 60

Patients with rheumatoid arthritis (RA) showed significantly (P < 0.01) increased numbers of granulocytes in their peripheral blood compared with normal donors and patients with osteoarthritis, and this finding correlated with interleukin-6 and C-reactive protein levels and active joint score. Then, 17 patients with RA were treated eight times in 4 weeks with a newly developed extracorporeal granulotrap column containing cellulose acetate beads (G-1 column). This column reduced granulocytes in the outflow blood by 50.2% compared with inflow counts. To evaluate the efficacy of G-1 therapy, 17 patients were followed for 12 weeks from the beginning of this therapy. The modified Lansbury index (LI) for monitoring RA activity significantly improved from a pretreatment mean score of 60.8% to a posttreatment score of 51.3%. The lowered scores were maintained up to 12 weeks after the initiation of therapy. Of the four LI items, tender and swollen joint scores showed the most significant improvement, with the tender joint score showing a particularly significant decrease throughout the study period. No serious side-effects were observed. These findings suggested that G-1 therapy was effective for RA.
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PMID:Improvement in rheumatoid arthritis following application of an extracorporeal granulotrap column, G-1. 871

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