title: Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinic of Orthopedics and Sports Orthopedics, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straβe 22, 81675 München, Germany. gollwitzer@bone-and-joint.org
authors.forename: Hans
authors.initials: H
authors.lastname: Gollwitzer
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: Peter M
authors.initials: PM
authors.lastname: Prodinger
authors.forename: Mark
authors.initials: M
authors.lastname: Peric
authors.forename: Burkhard
authors.initials: B
authors.lastname: Summer
authors.forename: Alexander
authors.initials: A
authors.lastname: Hapfelmeier
authors.forename: Belma
authors.initials: B
authors.lastname: Saldamli
authors.forename: Felix
authors.initials: F
authors.lastname: Pankow
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Eisenhart-Rothe
authors.forename: Andreas B
authors.initials: AB
authors.lastname: Imhoff
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Rainer
authors.initials: R
authors.lastname: Burgkart
authors.forename: Ingo J
authors.initials: IJ
authors.lastname: Banke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007595:Joint Prosthesis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D012372:ROC Curve; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D018709:Statistics, Nonparametric; D023083:beta-Defensins / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D016207:Cytokines; D023083:beta-Defensins; D002097:C-Reactive Protein; D054804:Cathelicidins