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Characterization of macrophage polarizing cytokines in the aseptic loosening of total hip replacements.

Authors
  • Jämsen, Eemeli
  • Kouri, Vesa-Petteri
  • Olkkonen, Juri
  • Cör, Andrej
  • Goodman, Stuart B
  • Konttinen, Yrjö T
  • Pajarinen, Jukka
Type
Published Article
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Publication Date
Sep 01, 2014
Volume
32
Issue
9
Pages
1241–1246
Identifiers
DOI: 10.1002/jor.22658
PMID: 24897980
Source
Medline
Keywords
License
Unknown

Abstract

Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle-induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT-PCR, the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and IL-17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN-γ or IL-4 could be identified. IL-17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up-regulation of IL-10, M-CSF, IL-8, CCL2-4, CXCL9-10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF-α, IL-1β, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri-implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines.

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