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 studied the ability of four clinically relevant particle species to stimulate human peripheral blood monocytes to release bone-resorbing agents, including interleukin-1 (both interleukin-1 alpha and interleukin-1 beta), interleukin-6, and prostaglandin E2. The species studied were titanium-6% aluminum-4% vanadium (TiAlV), commercially pure titanium, fabricated ultrahigh molecular weight polyethylene, and polyethylene retrieved from interfacial membranes of failed uncemented total hip arthroplasties. For all species, the mean size was less than 1 micron. Human peripheral blood monocytes were challenged with these particles in a uniform manner on the basis of surface area. Phorbol 12-myristate acetate, zymosan, and nonphagocytosable titanium particles served as controls. Stimulation of human monocytes is a function of the composition and concentration of particles. In this study, TiAlV particles appeared to be the most competent to elicit the synthesis and release of inflammatory mediators. Particles of commercially pure titanium and of fabricated ultrahigh molecular weight polyethylene also could induce the release of various cellular mediators, albeit at a lower level, whereas the particles of polyethylene retrieved from interfacial membranes were less stimulatory in these short-term in vitro experiments.
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PMID:Human monocyte response to particulate biomaterials generated in vivo and in vitro. 747 59

The alveolar macrophage (AM) is a critically important cell playing a prominent role in lung inflammation via the production of oxygen radicals, enzymes, arachidonic acid metabolites, and also a large panel of cytokines. Among interstitial lung disorders, silicosis and coal workers' pneumoconiosis (CWP) are the most widespread fibrotic lung diseases. Although their pathophysiology remains incompletely understood, several lines of evidence suggest the participation of cytokines produced by AMs at least in the initiation of the alveolitis. In vitro exposure of AMs (obtained from healthy subjects) to coal dust particles triggered a significant release of tumour necrosis factor (TNF) and interleukin-6, by comparison with titanium dioxide used as a biologically inert control dust. Moreover, it appeared that coal mine dust was more aggressive than similar concentrations of pure silica, suggesting that cytokine secretion induced by coal mine dust was not exclusively related to the presence of silica but resulted from a complex interaction between the different components. In silicosis and CWP, bronchoalveolar lavage showed a large influx of mononuclear phagocytes, with an increased spontaneous production of oxidants, fibronectin, neutrophil chemotactic factor, and also of interleukin-6 and TNF-alpha. This spontaneous cytokine release was associated with an increased cytokine messenger ribonucleic acid (mRNA) expression in the lungs of coal miners.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. 765 59

We investigated the relationship between the toxic effects of metal wear particles and their ability to stimulate the release of inflammatory mediators implicated in bone resorption. In vitro studies were carried out with use of rat peritoneal macrophages, which were exposed to either cobalt-chromium-alloy or titanium-aluminum-vanadium particles, milled from the metal components of hip prostheses. The particles were in the size-range of, and at concentrations similar to, those found in the tissues surrounding failed prostheses in humans. The titanium-aluminum-vanadium particles showed little toxicity even at high concentrations, while the cobalt-chromium particles were very toxic. The titanium-aluminum-vanadium particles induced significantly more release of prostaglandin E2 than did the cobalt-chromium particles, and this was true for a wide range of concentrations. Exposure to titanium-aluminum-vanadium increased the release of prostaglandin E2, interleukin-1, tumor necrosis factor, and interleukin-6. In contrast, exposure to cobalt-chromium particles was associated with a decreased release of prostaglandin E2 and interleukin-6, and it had little effect on the release of interleukin-1 and tumor necrosis factor.
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PMID:The differences in toxicity and release of bone-resorbing mediators induced by titanium and cobalt-chromium-alloy wear particles. 831 20

Titanium alloy particles were isolated from membranes obtained at revision arthroplasty. Addition of these retrieved particles to human monocytes/macrophages in cell culture resulted in morphologic change and metabolic activation. Cells exposed to these particles actively phagocytized the metallic debris, resulting in an increase in cytoplasm and a polarization of ingested metal. The metabolic response of the macrophages included increased release of prostaglandin E2, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha, and increased hexosaminidase activity. Increased release of interleukin-1 beta was maximal 6 to 12 hours after particle exposure. These data show that retrieved titanium alloy particles activate macrophages in vitro in an analogous fashion to that observed around failed arthroplasties.
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PMID:Human macrophage response to retrieved titanium alloy particles in vitro. 854 4

The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.
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PMID:Drug inhibition of the macrophage response to metal wear particles in vitro. 862

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

Cytokines produced by macrophages in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. The present study characterizes the response of human peripheral blood monocytes to titanium particles. Monocytes were obtained from volunteers and blood that had been donated to the American Red Cross and were cultured in the presence of titanium particles (one to three micrometers in diameter). There were consistent dose-dependent increases in the production of TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) protein, with the greatest stimulation generally observed with a concentration of 6 x 10(5) to 6 x 10(6) particles of titanium per milliliter. The level of TNF-alpha was the greatest (fifty to 1000 times greater than the control level) after eight hours of exposure to titanium particles; the level of IL-6 was two to five times greater than the control level after sixteen hours of exposure. These increases were similar to those observed after stimulation with lipopolysaccharide and depended on de novo synthesis rather than on release from intracellular stores. The production of TNF-alpha was inhibited in a dose-dependent manner by the translational inhibitor cycloheximide and the transcriptional inhibitor actinomycin D, indicating the requirement for both mRNA (messenger RNA) and protein synthesis for the induction of cytokine synthesis by titanium particles. Although the increase in the levels of cytokine mRNA in response to titanium was rapid (thirty to ninety minutes), the increase in the level of TNF-alpha mRNA preceded that of IL-6 mRNA. The level of TNF-alpha mRNA was the greatest at ninety minutes and the level of IL-6 mRNA was the greatest at three hours. After stimulation with titanium particles, the level of TNF-alpha mRNA was increased as much as fivefold and the level of IL-6 mRNA, as much as twelvefold.
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PMID:Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger RNA in human peripheral blood monocytes due to titanium particles. 875 10

This study was designed to define the role titanium debris plays in aseptic loosening. Macrophages exposed to commercially pure titanium (1-3 microns) exhibit the same mediator profile as those exposed to polymethylmethacrylate. This response consists of increased release of tumor necrosis factor but not prostaglandin E 2 or interleukin-1. Osteoblasts increase production of prostaglandin E 2 when exposed to media from titanium stimulated macrophages but not interleukin-6 or granulocyte macrophage colony stimulating factor. Media from macrophages exposed to titanium did not lead to bone resorption, as measured by calcium 45 release, in organ culture. The cellular response to titanium is characterized by release of tumor necrosis factor from macrophages and prostaglandin E 2 from osteoblasts exposed to the macrophage conditioned medium. A comparison of the results of this study with those of others involving exposure of macrophages in tissue culture suggests that titanium may not be as inflammatory as other particles in the aseptically loose joint.
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PMID:In vitro studies on the role of titanium in aseptic loosening. 880 99

The purpose of this study was to further define the cellular response to titanium and polymethylmethacrylate (PMMA) particles in aseptic loosening, and to determine if the use of pamidronate may be effective in inhibiting bone resorption associated with this response. Macrophages and osteoblasts were cocultured to simulate the environment around an aseptically loose prosthesis. Macrophages were plated on the bottom of six well plates and osteoblasts were plated on culture dish inserts, and placed into the wells with the macrophages. Incubation of macrophages with PMMA in this system led to release of prostaglandin E (PGE2), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-6 (IL-6). Incubation with titanium led to release of tumor necrosis factor (TNF) and IL-6. Exposure of calvaria to media from cells exposed to either PMMA or titanium led to release of calcium 45. Incubation of calvaria with pamidronate was able to inhibit release of calcium 45 associated with exposure to the macrophage/osteoblast/particle conditioned medium. Bone resorption at the interface between implant and bone is a consistent feature leading to loosening of orthopedic implants. By inhibiting bone resorption associated with the inflammatory response to implant particulates, pamidronate or other bisphosphonates may have clinical utility in the treatment or prevention or aseptic loosening.
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PMID:Inflammatory response to implant particulates in a macrophage/osteoblast coculture model. 884 7

Our aim was to determine whether in vitro studies would detect differences in the cellular response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 microm in diameter representative of those found adjacent to failed prostheses. Exposure of human monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10(7) particles/ml produced a mean prostaglandin E2 release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials.
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PMID:In vitro human monocyte response to wear particles of titanium alloy containing vanadium or niobium. 911 64


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