Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial

Osteoarthritis Cartilage. 2017 Sep;25(9):1443-1451. doi: 10.1016/j.joca.2017.05.009. Epub 2017 May 15.


Objective: Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years.

Design: We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA).

Results: Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated.

Conclusions: Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.

Keywords: Anterior cruciate ligament reconstruction; Biomarkers; Cytokines; Orthopedic surgery; Osteoarthritis; Synovial fluid.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Anterior Cruciate Ligament / surgery
  • Anterior Cruciate Ligament Injuries / metabolism
  • Anterior Cruciate Ligament Injuries / surgery*
  • Anterior Cruciate Ligament Reconstruction / methods*
  • Biomarkers / metabolism
  • Cytokines / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation Mediators / metabolism*
  • Male
  • Meniscus / surgery
  • Postoperative Period
  • Rupture / metabolism
  • Rupture / surgery
  • Synovial Fluid / metabolism*
  • Young Adult


  • Biomarkers
  • Cytokines
  • Inflammation Mediators