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Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty

BACKGROUND: All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s), particularly T-helper type 1 (...

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Autores principales: Hallab, Nadim James, Caicedo, Marco, Finnegan, Alison, Jacobs, Joshua J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275232/
https://www.ncbi.nlm.nih.gov/pubmed/18271968
http://dx.doi.org/10.1186/1749-799X-3-6
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author Hallab, Nadim James
Caicedo, Marco
Finnegan, Alison
Jacobs, Joshua J
author_facet Hallab, Nadim James
Caicedo, Marco
Finnegan, Alison
Jacobs, Joshua J
author_sort Hallab, Nadim James
collection PubMed
description BACKGROUND: All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s), particularly T-helper type 1 (Th1) responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs). We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis. METHODS: Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8) were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15) with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months) were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49–80). Group 1 subjects' lymphocyte proliferation response to Aluminum(+3), Cobalt(+2), Chromium(+3), Copper(+2), Iron(+3), Molybdenum(+5), Manganeese(+2), Nickel(+2), Vanadium(+3 )and Sodium(+2 )chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM) was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl(3), 0.1 mM NiCl(2), 0.1 mM CoCl(2 )and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence. RESULTS: Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p < 0.03). Of the 15 metal ion-challenged subjects with well functioning total hip arthroplasties, 7 demonstrated a proliferative response to Chromium, Nickel, Cobalt and/or Titanium (as defined by a statistically significant >2 fold stimulation index response, p < 0.05) and were designated as metal-reactive. Metals such as Cobalt, Copper, Manganese, and Vanadium were toxic at concentrations as low as 0.5 mM while other metals, such as Aluminum, Chromium, Iron, Molybdenum, and Nickel, became toxic at much higher concentrations (>10 mM). The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes releasing IFN-gamma and IL-4, respectively) between those total hip arthroplasty subjects which demonstrated metal-reactivity and those that did not, indicated a Th1 type (IFN-gamma) pro-inflammatory response. CONCLUSION: Elevated proliferation and production of IFN-gamma to metals in hip arthroplasty subjects' lymphocytes indicates that a Th1 (vs. Th2) type response is likely associated with any metal induced reactivity. The involvement of an elevated and specific lymphocyte response suggests an adaptive (macrophage recruiting) immunity response to metallic implant debris rather than an innate (nonspecific) immune response.
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spelling pubmed-22752322008-03-26 Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty Hallab, Nadim James Caicedo, Marco Finnegan, Alison Jacobs, Joshua J J Orthop Surg Research Article BACKGROUND: All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s), particularly T-helper type 1 (Th1) responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs). We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis. METHODS: Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8) were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15) with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months) were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49–80). Group 1 subjects' lymphocyte proliferation response to Aluminum(+3), Cobalt(+2), Chromium(+3), Copper(+2), Iron(+3), Molybdenum(+5), Manganeese(+2), Nickel(+2), Vanadium(+3 )and Sodium(+2 )chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM) was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl(3), 0.1 mM NiCl(2), 0.1 mM CoCl(2 )and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence. RESULTS: Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p < 0.03). Of the 15 metal ion-challenged subjects with well functioning total hip arthroplasties, 7 demonstrated a proliferative response to Chromium, Nickel, Cobalt and/or Titanium (as defined by a statistically significant >2 fold stimulation index response, p < 0.05) and were designated as metal-reactive. Metals such as Cobalt, Copper, Manganese, and Vanadium were toxic at concentrations as low as 0.5 mM while other metals, such as Aluminum, Chromium, Iron, Molybdenum, and Nickel, became toxic at much higher concentrations (>10 mM). The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes releasing IFN-gamma and IL-4, respectively) between those total hip arthroplasty subjects which demonstrated metal-reactivity and those that did not, indicated a Th1 type (IFN-gamma) pro-inflammatory response. CONCLUSION: Elevated proliferation and production of IFN-gamma to metals in hip arthroplasty subjects' lymphocytes indicates that a Th1 (vs. Th2) type response is likely associated with any metal induced reactivity. The involvement of an elevated and specific lymphocyte response suggests an adaptive (macrophage recruiting) immunity response to metallic implant debris rather than an innate (nonspecific) immune response. BioMed Central 2008-02-13 /pmc/articles/PMC2275232/ /pubmed/18271968 http://dx.doi.org/10.1186/1749-799X-3-6 Text en Copyright © 2008 Hallab et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hallab, Nadim James
Caicedo, Marco
Finnegan, Alison
Jacobs, Joshua J
Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
title Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
title_full Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
title_fullStr Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
title_full_unstemmed Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
title_short Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
title_sort th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275232/
https://www.ncbi.nlm.nih.gov/pubmed/18271968
http://dx.doi.org/10.1186/1749-799X-3-6
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