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Antimicrobial Peptides and Proinflammatory Cytokines in Periprosthetic Joint Infection
Hans Gollwitzer, MD1; Yvonne Dombrowski, PhD2; Peter M. Prodinger, MD1; Mark Peric, PhD2; Burkhard Summer, PhD2; Alexander Hapfelmeier, Dipl-Stat1; Belma Saldamli, DMD1; Felix Pankow, Cand. Med.1; Rüdiger von Eisenhart-Rothe, MD1; Andreas B. Imhoff, MD1; Jürgen Schauber, MD2; Peter Thomas, MD2; Rainer Burgkart, MD1; Ingo J. Banke, MD1
1 Clinic of Orthopedics and Sports Orthopedics (H.G., P.M.P., B.S., F.P., R.v.E.-R., R.B., and I.J.B.), Division of Orthopedic Sports Surgery (A.B.I.), and the Institute of Medical Statistics and Epidemiology (A.H.), Klinikum rechts der Isar, Technische Universität München, Ismaninger Straβe 22, 81675 München, Germany. E-mail address for H. Gollwitzer: gollwitzer@bone-and-joint.org
2 Department of Dermatology and Allergy, Ludwig-Maximilians-University, Frauenlobstraβe 9-11, 80337 München, Germany
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Investigation performed at the Clinic of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technische Universität München, München, Germany

Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Apr 03;95(7):644-651. doi: 10.2106/JBJS.L.00205
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Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection.


Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the “gold standard” for the diagnosis of infection.


The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75).


The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.

Level of Evidence: 

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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