nanoGold and μGold inhibit autoimmune inflammation: a reviewWhile gold was once considered inert, gold implants in animals and humans have been found to release gold ions into the surrounding tissue. Danscher and Rasmussen review and summarise the recent findings of various studies regarding the application of metallic gold particles for the treatment of inflammation and its consequences and associated processes on the cellular level. The authors differentiate in size between (a) treatment with injected gold microparticles > 20 μm (and gold macro-implants [as used in gold implantation]) on the one hand and (b) gold nanoparticles as used in other therapies on the other. In contrast to the latter, the former are so large that macrophages cannot engulf them and instead start secreting cyanide compounds dissolving the gold. (a) Gold microparticles > 20 μm (and gold macro-implants [like in gold implantation]) are reported to stay where injected [or implanted] in the tissue, and it has been shown that gold ions are released from them by macrophages and taken up by the cells in the vicinity of a few millimetres. Thus, as the authors imply, no gold ions are spread to gold-sensitive organs, thereby excluding any toxic effects. Proteins are adsorbed to the gold surface and form a nanometre-thick so-called “dissolution” membrane. Macrophages settling on the gold surface oxidate gold atoms into gold ions Au+. They secrete cyanide ions (CN)– into the membrane and dissolve the gold ions (Au+), creating dicyanoaurate ions [Au(CN)2]–. These diffuse from the membrane into the intercellular space and are responsible for the anti-inflammatory effects of metallic gold; there they bind to soluble and membrane-bound proteins containing sulphur and are taken up and concentrated in the lysosomes of the cells. The released gold ions can thus be traced in macrophages, mast cells, fibroblasts, and fibres, which are also known to take up gold ions of injected aurothiomalate [gold compound used for reducing inflammation related to rheumatoid arthritis]. The release of gold ions may be higher in inflammatory tissue compared to normal tissue. The release of gold ions from gold micro- or macroparticles may continue for years, thus influencing the extracellular environment continuously. The process of slow dissolution of gold particles by macrophages has been named “dissolucytosis”. Regarding the mode of action, it has been found that in the synovial tissues and the fluid around inflamed joints there is an unsually high amount of the protein HMGB1 (high-mobility group box 1 chromosomal protein). While in the cell nucleus HMGB1 is involved in the transcription of DNA to RNA, it stimulates the immune system and induces inflammation when released from the cell. Gold ions (from aurothiomalate) were found to inhibit the release of HMGB1 from the nucleus (by interfering with the activity of the helper molecules IFN and NO), thus reducing its amount in the extracellular space and lessening inflammation. (b) Nanometre-sized gold particles, however, due to their small size are spread throughout the body. There the bio-released gold ions can affect multitudes of cells as in the case of gold-containing drugs. Macrophages and other phagocytotic cells engulf and transport the nanoparticles and remove them after a short period. New cells take their place. For this reason, repeated treatment (such as for rheumatoid arthritis) is necessary (whereas in case of gold microparticles the new cells are now exposed to the gold still in place nearby). While there is a temporary and beneficial effect of gold nanoparticles on autoimmune inflammation and gold nanoparticles may be less acutely toxic than gold-containing drugs, the authors quote a study of the acute and chronic administration of gold nanoparticles that has found that these cause DNA damage in the cerebral cortex of adult rats. In contrast, no gold ions from gold microparticles or macro-implants are spread to gold-sensitive organs so that toxic effects are excluded here. To sum up, the authors clarify that and how pure metallic gold in inflammatory tissues mitigates inflammatory processes and may even stop inflammation. They hope that more clinical studies will soon support the experimental and empirical evidence.
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