The immunobiology of cobalt

Lawrence, Helen; Deehan, David J.; Holland, J; Kirby, John A.; Tyson-Capper, AJ

doi:10.1302/0301-620x.96b9.33476

Cited by 32 publications

(16 citation statements)

References 40 publications

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“…TLR4-expressing MonoMac 6 cells have previously been shown to upregulate IL-8 secretion and expression when challenged with cobalt ions [ 14 ] and were therefore selected as an in vitro cell model for this study, using IL-8 as a marker of TLR4 activation. MonoMac 6 cells were pre-treated with 10μg/ml MAb2-hTLR4 for 1h prior to 16h stimulation with 0.75mM CoCl 2 or 100ng/ml LPS.…”

Section: Resultsmentioning

confidence: 99%

“…Cobalt chloride hexahydrate (CoCl 2 ) was diluted in complete cell culture medium and used at 0.75mM, a physiological concentration optimised in a previous study [ 14 ]. TLR4-specific LPS (from E. coli serotype J5, Alexis Biochemicals, San Diego, USA) was used at 100ng/ml as a positive control for receptor activation.…”

Section: Methodsmentioning

confidence: 99%

“…Enzyme-linked immunosorbent assays (ELISA) were used to quantify cytokine secretion by MonoMac 6 cells. IL-8 secretion was quantified using a Human IL-8 ELISA kit (Peprotech, London, UK) as described previously [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies by our group and others have shown that cobalt ions generated by MoM hip articulation can activate the innate immune receptor Toll-like receptor 4 (TLR4) [ 11 - 14 ] which is most commonly known as the receptor for Gram negative bacterial lipopolysaccharide (LPS). Cobalt-mediated TLR4 activation increases the secretion of pro-inflammatory cytokines such as interleukin-8 (IL-8, chemokine (C-X-C motif) ligand 8 or CXCL8), interleukin-6 (IL-6) and chemokine (C-X-C motif) ligand 10 (CXCL10) in macrophages and endothelial cells [ 11 , 14 ]. A small molecule TLR4 antagonist, CLI-095, is able to prevent these responses [ 14 ] but its therapeutic use is limited because of its intracellular mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

“…Cobalt-mediated TLR4 activation increases the secretion of pro-inflammatory cytokines such as interleukin-8 (IL-8, chemokine (C-X-C motif) ligand 8 or CXCL8), interleukin-6 (IL-6) and chemokine (C-X-C motif) ligand 10 (CXCL10) in macrophages and endothelial cells [ 11 , 14 ]. A small molecule TLR4 antagonist, CLI-095, is able to prevent these responses [ 14 ] but its therapeutic use is limited because of its intracellular mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

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Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation

et al. 2016

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Cobalt-chrome alloy is a widely used biomaterial in joint replacements, dental implants and spinal rods. Although it is an effective and biocompatible material, adverse reactions to metal debris (ARMD) have arisen in a minority of patients, particularly in those with metal-on-metal bearing hip replacements. There is currently no treatment for ARMD and once progressive, early revision surgery of the implant is necessary. Therapeutic agents to prevent, halt or reverse ARMD would therefore be advantageous.Cobalt ions activate Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to bacterial lipopolysaccharide (LPS) resulting in the production of pro-inflammatory cytokines and chemokines. We hypothesised that anti-TLR4 neutralising antibodies, reported to inhibit TLR4-mediated inflammation, could prevent the inflammatory response to cobalt ions in an in vitro macrophagecell culture model.This study shows that a monoclonal anti-TLR4 antibody inhibited cobalt-mediated increases in pro-inflammatory IL8, CCL20 and IL1A expression, as well as IL-8 secretion. In contrast, a polyclonal antibody did not prevent the effect of cobalt ions on either IL-8 or IL1A expression, although it did have a small effect on the CCL20 response. Interestingly, both antibodies inhibited cobalt-mediated neutrophil migration although the greater effect was observed with the monoclonal antibody.In summary our data shows that a monoclonal anti-TLR4 antibody can inhibit cobalt-mediated inflammatory responses while a polyclonal antibody only inhibits the effect of specific cytokines. Anti-TLR4 antibodies have therapeutic potential in ARMD although careful antibody design is required to ensure that the LPS response is preserved.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation

et al. 2016

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The biological response to orthopaedic implants for joint replacement: Part I: Metals

Gibon

Amanatullah

Loi

et al. 2016

J. Biomed. Mater. Res.

107

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Joint replacement is a commonly performed, highly successful orthopaedic procedure, for which surgeons have a large choice of different materials and implant designs. The materials used for joint replacement must be both biologically acceptable to minimize adverse local tissue reactions, and robust enough to support weight bearing during common activities of daily living. Modern joint replacements are made from metals and their alloys, polymers, ceramics, and composites. This review focuses on the biological response to the different biomaterials used for joint replacement. In general, modern materials for joint replacement are well tolerated by the body as long as they are in bulk (rather than in particulate or ionic) form, are mechanically stable and noninfected. If the latter conditions are not met, the prosthesis will be associated with an acute/chronic inflammatory reaction, peri-prosthetic osteolysis, loosening and failure. This article (Part 1 of 2) is dedicated to the use of metallic devices in orthopaedic surgery including the associated biological response to metallic byproducts is a review of the basic science literature regarding this topic.

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In vitro evaluation of human myoblast function after exposure to cobalt and chromium ions

Laumonier

Ruffieux

Paccaud

et al. 2020

Journal Orthopaedic Research

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The replacement of a native hip joint by a metal‐on‐metal prosthesis may induce deleterious inflammatory side effects that are associated with the release of wear particles and metal ions. These events are referred to the adverse reaction to metal debris (ARMD) and the adverse local tissue reaction (ALTR). While wear particles seem involved in ARMD, the role of metal ions in ALTR and their impact on myoblasts, located in the prosthesis vicinity, has not been fully identified. To clarify this issue we investigated, using an in vitro culture system, the effect of cobalt and/or chromium ions (Co2+ and/or Cr3+) on human myoblast proliferation, cellular differentiation, and inflammatory marker expression. Freshly isolated human myoblasts were cultured in media supplemented with graded concentrations of Co2+ and/or Cr3+. Co2+ induced a concentration‐dependent decrease of both myoblast viability and myogenic differentiation while Cr3+ did not. Co2+ or Co2+/Cr3+ also induced the upregulation of ICAM‐1, whereas HLA‐DR expression was unaffected. Moreover, allogenic monocytes induced the synergistic increase of Co2+‐induced ICAM‐1 expression. We also found that Co2+ stabilized HIF‐1α and increased TLR4, tumor necrosis factor‐alpha (TNF‐α), and interleukin 1β (IL‐1β) expression in a dose and time‐dependent manner in human myoblasts. This study showed that Co2+, but not Cr3+, was toxic toward myoblasts and induced, in the surviving cells, expression of inflammatory markers such as ICAM‐1, TLR4, TNF‐α, and IL‐1β. This suggests that Co2+, most efficiently in the presence of monocytes, may be a key inducer of ALTR, which may, if severe and long‐lasting, eventually result in prosthesis loosening.

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The immunobiology of cobalt

Cited by 32 publications

References 40 publications

Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation

Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation

The biological response to orthopaedic implants for joint replacement: Part I: Metals

In vitro evaluation of human myoblast function after exposure to cobalt and chromium ions

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