Biomed Res Int. 2014;2014:426893.

Early intraarticular complement activation in ankle fractures.

Schmal H1, Salzmann GM1, Niemeyer P1, Langenmair E1, Guo R2, Schneider C2, Habel M2, Riedemann N2.
  • 1Department of Orthopedics and Trauma Surgery, Albert-Ludwigs University Medical Center Freiburg, 79106 Freiburg, Germany.
  • 2Inflarx, 07745 Jena, Germany.



Purpose: Cytokine regulation is believed to influence long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Intraarticular inflammation accompanied by complement activation following fractures is thought to initiate the development of osteoarthritis.

Methods: Patients with an ankle dislocation fracture (average age 39±21 years) were included in a prospective case series. Based on a matched-pair analysis synovial levels were compared to patients with a grade 2 osteochondritis dissecans (OCD) lesion of the ankle (intact cartilage surface). A total of 20 patients were included in the study. Joint effusions were collected during external fixation or arthroscopy. Fluid analysis was done by ELISA for total protein content, aggrecan, bFGF, IL-1β, IGF-1, and the complement components C3a, C5a and C5b-9. Data was supplemented by epidemiological parameters. Furthermore, the composition of cells within the effusion was investigated using the clinical routine analysis.

Results:  The time periods between occurrence of fracture and collection of effusion were only significantly associated with synovial aggrecan and C5b-9 levels (P  <  0.001). Furthermore, synovial expressions of both proteins correlated with each other (P < 0.001). Although IL-1 β expression was relatively low, intra-articular levels correlated with C5a (P  <  0.01) and serological C-reactive protein concentrations 2 days after surgery (P < 0.05). Joint effusions were initially dominated by neutrophils, but the portion of monocytes constantly increased reaching 50% at day 6 after fracture (P < 0.02). Whereas aggrecan and IL-1β concentrations were not different in fracture and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P < 0.01). Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures.



Cells_1Fig 1. The relation of leucocytes in effusion and leucocytes in blood decreased over time showing a statistically significant correlation (R=-0.98, p=0.011, dashed line). In parallel, the percentage of monocytes in joint flushes increased over time starting with 9.5% 4 hours after trauma (90.5% neutrophils), reaching 50.4% 144 hours (49.6% neutrophils) following injury (R=0.97, p=0.013, solid line).
Complement_2 Fig 2. Comparison of C3a levels (A, p=0.0003), C5a levels (B, p=0.0018) and C5b-9 levels (C, p=0.0013) in patients with ankle dislocation fractures and patients suffering from an OCD grade 2. The difference was statistically significant for all comparisons.


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