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Local and Systemic Activation of the Mononuclear Phagocyte System in Aseptic Loosening of Total Hip Arthroplasty

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Abstract

Introduction

Osteoarticular prosthesis loosening involves recruitment, activation, and differentiation of mononuclear phagocytes, with a complex and still unclear interplay of local and systemic inflammation. We hypothesized that aseptic hip prosthesis loosening is bound to a coordinated systemic and local activation of the mononuclear phagocyte system (MPS), which can be demonstrated by simultaneous assessment of both compartments. We, therefore, compared systemic and synovial inflammatory cytokines, circulating monocyte activation state, and synovial fluid (SF) ability to induce osteoclastic differentiation.

Materials and Methods

Twenty-seven patients undergoing total hip replacement for aseptic loosening were compared to 30 patients receiving total hip prosthesis for primary osteoarthritis.

Results and Discussion

SF from aseptic loosening patients induced a more effective osteoclast-like differentiation of monocytic THP-1 cells in vitro and a proinflammatory pattern of cytokine production in these osteoclast-like cultures. On the contrary, SF from osteoarthritis patients did not favor osteoclastogenesis and exerted an anti-inflammatory effect through IL-10 upregulation and TNF-α inhibition. Peripheral blood monocytes of aseptic loosening patients were primed for activation, with higher TNF-α responses than their counterparts in the osteoarthritis group. Finally, cytokine enrichment in SF versus serum was observed in both patient groups: a fivefold increase in synovial TNF-α in aseptic loosening patients and a 14-fold increase in synovial IL-10 in osteoarthritis patients. The TNF-α/IL-10 ratio was elevated in both systemic and synovial settings from aseptic loosening patients with respect to osteoarthritis patients.

Conclusion

Taken together, our results demonstrate the integrated activation of the MPS and suggest the possible use of cytokines in the laboratory workup of prosthesis aseptic loosening.

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Abbreviations

GM-CSF:

granulocyte macrophage colony-stimulating factor

IL:

interleukin

LPS:

lipopolysaccharide (endotoxin)

M-CSF:

macrophage colony-stimulating factor

MPS:

mononuclear phagocyte system

OA:

osteoarthritis

O/THP-1:

osteoclast-differentiated THP-1 cells

RANK:

receptor activator of NFκB

RANKL:

receptor activator of NFκB ligand

SF:

synovial fluid

Th:

helper T cell

THR:

total hip revision

TGFβ1:

transforming growth factor-β1

TNF-α:

tumor necrosis factor-α

TRAP:

tartrate-resistant acid phosphatase

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Authors and Affiliations

  1. Assistance Publique Hopitaux de Marseille, Aix-Marseille University, Department of Orthopedic Surgery, Sainte-Marguerite Hospital, 270 bd Sainte Marguerite, BP 29, 13274, Marseille cedex 09, France

    Xavier Flecher & Jean-Noel Argenson

  2. Assistance Publique Hopitaux de Marseille, Aix-Marseille University, Immunology Laboratory, INSERM UMR 600, CNRS UMR 6212, Conception Hospital, 147 bd Baille, 13005, Marseille, France

    Christelle Rolland, Philippe Robert, Pierre Bongrand & Joana Vitte

  3. Aix-Marseille University, CNRS-USR 2164, Laboratory of Aerodynamic and Biomechanic Motion, 163 avenue de Luminy, case 918, 13288, Marseille, France

    Emmanuel Rixrath & Sylvie Wendling

Authors
  1. Xavier Flecher
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  2. Christelle Rolland
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  3. Emmanuel Rixrath
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  8. Joana Vitte
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Correspondence to Joana Vitte.

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Flecher, X., Rolland, C., Rixrath, E. et al. Local and Systemic Activation of the Mononuclear Phagocyte System in Aseptic Loosening of Total Hip Arthroplasty. J Clin Immunol 29, 681–690 (2009). https://doi.org/10.1007/s10875-009-9305-9

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  • DOI: https://doi.org/10.1007/s10875-009-9305-9

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