Influence of metal ions on human lymphocytes and the generation of titanium-specific T-lymphocytes

Chan, Erwin; Cadosch, Dieter; Gautschi, Oliver; Sprengel, Kai; Filgueira, Luis

doi:10.5301/jabb.2011.8567

Cited by 23 publications

(17 citation statements)

References 43 publications

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“…As indicators of DTH, IL-2 and IFN-γ levels were statistical significantly increased in the AL (+) group compared to the AL (−), supporting the involvement of a Th1 cell response in AL. This is consistent with other studies, showing lymphocyte reactivity to implant related metals and production of Th1-specific cytokines (IFN-γ and IL-2), and even the generation of metal specific T cells [41,42]. Macrophages are capable of producing IFN-γ but abundant evidence suggests that T cells and natural killer (NK) cells are the major sources of IFN-γ [3,43,44].…”

Section: Discussionsupporting

confidence: 90%

Cytokine Profile in Patients with Aseptic Loosening of Total Hip Replacements and Its Relation to Metal Release and Metal Allergy

Christiansen

Münch

Bonefeld

et al. 2019

JCM

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Metal release from total hip replacements (THRs) is associated with aseptic loosening (AL). It has been proposed that the underlying immunological response is caused by a delayed type IV hypersensitivity-like reaction to metals, i.e., metal allergy. The purpose of this study was to investigate the immunological response in patients with AL in relation to metal release and the prevalence of metal allergy. THR patients undergoing revision surgery due to AL or mechanical implant failures were included in the study along with a control group consisting of primary THR patients. Comprehensive cytokine analyses were performed on serum and periimplant tissue samples along with metal analysis using inductive coupled plasma mass spectrometry (ICP-MS). Patient patch testing was done with a series of metals related to orthopedic implant. A distinct cytokine profile was found in the periimplant tissue of patients with AL. Significantly increased levels of the proinflammatory cytokines IL-1β, IL-2, IL-8, IFN-γ and TNF-α, but also the anti-inflammatory IL-10 were detected. A general increase of metal concentrations in the periimplant tissue was observed in both revision groups, while Cr was significantly increased in patient serum with AL. No difference in the prevalence of metal sensitivity was established by patch testing. Increased levels of IL-1β, IL-8, and TNF-α point to an innate immune response. However, the presence of IL-2 and IFN-γ indicates additional involvement of T cell-mediated response in patients with AL, although this could not be detected by patch testing.

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Section: Discussionsupporting

confidence: 90%

Cytokine Profile in Patients with Aseptic Loosening of Total Hip Replacements and Its Relation to Metal Release and Metal Allergy

Christiansen

Münch

Bonefeld

et al. 2019

JCM

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“…The poor water solubility of titanium is often considered as an indicator of its biological inertness. However, studies and case reports of patients with malfunctioning titanium implants reveal a range of adverse effects associated with this metal, including inflammation [49], pain [8], cytotoxicity [50,51], metal allergy [52,53], genotoxicity [54], carcinogenicity [55] and implant failure [56]. The most widely researched effects of titanium are those on the bone cells-osteoblasts (bone-forming) and osteoclasts (bone-resorbing) [42,53,57,58].…”

Section: Adverse Effects Of Titanium Debrismentioning

confidence: 99%

Blood titanium level as a biomarker of orthopaedic implant wear

Swiatkowska

Martin

Hart

2019

Journal of Trace Elements in Medicine and Biology

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Background: Joint replacement implants are usually manufactured from cobalt-chromium or titanium alloys. After the device is implanted, wear and corrosion generate metal particles and ions, which are released into local tissue and blood. The metal debris can cause a range of adverse local and systemic effects in patients. Research problem: In the case of cobalt and chromium, a blood level exceeding 7 µg L-1 indicates potential for local toxicity, and a failing implant. It has been repeatedly suggested in the literature that measurement of titanium could also be used to assess implant function. Despite an increasing interest in this biomarker, and growing use of titanium in orthopaedics, it is unclear what blood concentrations should raise concerns. This is partly due to the technical challenges involved in the measurement of titanium in biological samples. Aim: This Review summarises blood/serum titanium levels associated with well-functioning and malfunctioning prostheses, so that the prospects of using titanium measurements to gain insights into implant performance can be evaluated. Conclusion: Due to inter-laboratory analytical differences, reliable conclusions regarding "normal" and "abnormal" titanium levels in patients with orthopaedic implants are difficult to draw. Diagnosis of symptomatic patients should be based on radiographic evidence combined with blood/serum metal levels.

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“…Single titanium ions are not antigenic, as they are too small, but they are able to form complexes with proteins to form a hapten [175]. A recent study was able to demonstrate the strong and specific antigenicity of titanium ions released by biocorrosion, by showing that titanium-specific T lymphocytes are generated when human monocyte-derived dendritic cells are exposed to titanium ions [177]. However, there is still a need to investigate and analyze the extent to which other metals in metallic implants form immunogenic complexes or how they become antigenic and are presented to T lymphocytes.…”

Section: Pathophysiology Of Metal Hypersensitivity Reactionsmentioning

confidence: 98%

Hypersensitivity Reactions to Implanted Metal Devices: Facts and Fictions

2016

J Investig Allergol Clin Immunol

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The use of metals in the medical field has become increasingly prevalent over the past few decades. Patients find themselves being exposed to metals in a variety of ways, ranging from external exposure to instruments such as the stainless steel in surgical blades to internal exposure via medical devices being implanted in their bodies. There has been growing interest in the possibility of developing hypersensitivity reactions to constituent metals in medical implant devices, both in cutaneous and systemic forms. Hypersensitivity reactions to metals are uncommon, but they are reported and require appropriate evaluation and management, particularly if they are symptomatic. In view of the lack of consensus in the field on the appropriate steps to evaluate and manage patients with suspected metal hypersensitivity reactions, this review aims to analyze current evidence on hypersensitivity reactions to metallic implants in orthopedic surgery, endovascular surgery, obstetrics and gynecology, and dental surgery. Key words: Metal hypersensitivity. Metallic implants. ResumenEl empleo de metales dentro de la medicina ha ido aumentando de forma progresiva en las últimas décadas. Los pacientes se exponen a metales de diferentes formas desde fuentes externas, como instrumental quirúrgico como el presente en las hojas de acero de los bisturíes, hasta implantes metálicos. Como consecuencia de ello se está produciendo un interés creciente por la posibilidad de desarrollar reacciones de hipersensibilidad a metales presentes en los materiales y objetos implantados, tanto en forma de reacciones cutáneas como sistémicas. Las reacciones de hipersensibilidad a metales no son frecuentes, pero pueden desarrollarse, y por ello, requieren de un diagnóstico y tratamiento adecuado, especialmente en aquellos pacientes que desarrollen síntomas. No existe un consenso en el proceso diagnóstico ni en el tratamiento de estas reacciones en los pacientes con sospecha de alergia a metales. Esta revisión tiene por objeto actualizar la evidencia existente sobre las reacciones de hipersensibilidad a implantes metálicos en cirugía ortopédica, cirugía endovascular, cirugía obstétrica y ginecológica (OB-GYN) así como la dental. Palabras clave: Hipersensibilidad a metales. Implantes metálicos.

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Influence of metal ions on human lymphocytes and the generation of titanium-specific T-lymphocytes

Abstract: This study showed that mDC exposed to Titanium (IV) are able to induce the generation of Titanium (IV)-specific T-lymphocytes, demonstrating the strong and specific antigenicity of Titanium (IV) ions released by biocorrosion.

Cited by 23 publications

References 43 publications

Cytokine Profile in Patients with Aseptic Loosening of Total Hip Replacements and Its Relation to Metal Release and Metal Allergy

Cytokine Profile in Patients with Aseptic Loosening of Total Hip Replacements and Its Relation to Metal Release and Metal Allergy

Blood titanium level as a biomarker of orthopaedic implant wear

Hypersensitivity Reactions to Implanted Metal Devices: Facts and Fictions

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