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

Rune J Christiansen,Jacob P Thyssen,Henrik J Münch,Charlotte M Bonefeld,Carsten Geisler,Kjeld Søballe,Morten S Jellesen,Stig S Jakobsen,Jens J Sloth

doi:10.3390/jcm8081259

Abstract

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.

Highlights

IntroductionThe etiology of aseptic loosening (AL) is multifactorial and yet to be fully understood, evidence suggest that the predominant cause of AL is due to a macrophage-driven chronic inflammatory response initiated by implant wear [1,3,4,5]
Key mediators of osteolysis have been identified as pro-inflammatory cytokines like interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α secreted by activated macrophages
We found a highly increased cytokine profile in patients with aseptic loosening (AL), with a statistical significant increase of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ and TNF-α when compared to the AL (+) and the control group

Summary

Introduction

The etiology of AL is multifactorial and yet to be fully understood, evidence suggest that the predominant cause of AL is due to a macrophage-driven chronic inflammatory response initiated by implant wear [1,3,4,5]. This adverse tissue reaction is associated with the innate immune system and can lead to the bone degrading state of osteolysis, subsequently resulting in implant failure by AL. Interferon (IFN)-γ is another important immune regulatory cytokine implicated in bone resorption and in inflammation progression and cell mediated immunity [12,13]

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Discussion

Conclusion