Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial

Ida C Helmark, Ulla R Mikkelsen, Jens Børglum, Anders Rothe, Marie C H Petersen, Ove Andersen, Henning Langberg, Michael Kjaer, Ida C Helmark, Ulla R Mikkelsen, Jens Børglum, Anders Rothe, Marie C H Petersen, Ove Andersen, Henning Langberg, Michael Kjaer

Abstract

Introduction: The microdialysis method was applied to the human knee joint with osteoarthritis (OA) in order to reveal changes in biochemical markers of cartilage and inflammation, intraarticularly and in the synovium, in response to a single bout of mechanical joint loading.

Methods: Thirty-one female subjects with OA of the knee were randomized to non-exercise (NEx) or exercise (Ex) groups. Following acute resistance exercise (25 sets of 10 repetitions at 60% of 1 Repetition Maximum) or none (NEx), peripheral nerve blocks just below the inguinal ligament were applied and two microdialysis catheters were positioned in two different compartments, intraarticularly and peri-synovially. The microdialysis catheters were perfused at a slow rate (2 μl/minute) with a solution of Ringer-acetate and radioactively labelled glucose allowing for determination of relative recovery (RR) and calculation of interstitial concentrations of inflammatory and cartilage biomarkers over a three-hour period.

Results: A significant increase of Interleukin (IL) -10 was discovered in both positions of the knee in the Ex group over the three hours post exercise, whereas IL-10 remained stationary over time in the NEx group. IL-6 and IL-8 displayed significant increases over time regardless of group and position of the catheter. Cartilage oligomeric matrix protein (COMP) decreased intraarticularly in the post exercise period in the Ex group compared to the NEx group.

Conclusions: Exercise caused an increase in both intraarticular and peri-synovial concentrations of IL-10 in a group of human females with knee OA. This suggests a positive effect of exercise on a chondroprotective anti-inflammatory cytokine response in patients with knee OA and might contribute to explaining the beneficial effect that exercise has on OA.

Trial registration: NCT01090375.

Figures

Figure 1
Figure 1
Test day. Subjects met at either 8.30 a.m. (Ex) or 9.30 a.m. (NEx) according to randomization. Following exercise or none, blood and urine samples were taken (T1) and regional anaesthesia was applied. Two catheters were hereafter positioned in the suprapatellar recess and in the sub synovial tissue on the medial side of the knee, respectively. Catheters were removed after three hours of microdialysis. The removal was preceded by blood and urine samples (T2). Samples of dialysate were collected every 30 minutes. Relative recovery was calculated for every sample and samples were later pooled (t1 = Sample 1 to 3; t2 = Sample 4 to 6).
Figure 2
Figure 2
Schematic illustration of the positioning of the catheters in the knee joint with osteoarthritis. The intraarticular catheter is placed in the suprapatellar recess and the peri-synovial catheter in the medial part of the knee capsule. A precision pump perfuses the catheters at a selected rate of 2 μl/min.
Figure 3
Figure 3
Concentrations of IL-6, IL-8, IL-10 and TNF-α. Intraarticular (left panel) and peri-synovial (right panel) concentrations in the NEx and Ex groups at T1 and T2. Each point represents a mean (when run in duplicate) of the measured values and each connecting line represents a subject with before/after values. IL-10 increased significantly in the Ex group in both compartments (*P < 0.05), but remained stationary in the NEx group. Significant increases regardless of exercise are seen for IL-6 and IL-8 in both positions and also for TNF-α intraarticularly (*P < 0.05), whereas TNF-α increased peri-synovially in the Ex group but not in the Ex group. (i.a., intraarticular; syn, peri-synovial).
Figure 4
Figure 4
Serum concentrations of COMP and Aggrecan in the NEx and Ex groups at T1 and T2. Each point represents a mean of the measured values and each connecting line represents a subject with before/after values. A significant decrease over time was found in both groups for both markers, regardless of exercise (*P < 0.05).
Figure 5
Figure 5
Intraarticular (top row) and peri-synovial (bottom row) concentrations of COMP and Aggrecan. Each point represents a mean of the measured values and each connecting line represents a subject with before/after values. COMP remained stationary in the NEx group in both compartments and in the Ex group peri-synovially over time, but decreased in the Ex group intraarticularly, whereas Aggrecan concentrations decreased significantly from T1 to T2 in both positions regardless of exercise (*P < 0.05).
Figure 6
Figure 6
Creatinine-corrected urinary concentrations of Aggrecan and CTX-II in NEx and Ex groups at T1 and T2. Each point represents a mean of the measured values and each connecting line represents a subject with before/after values. The Ex group had a significantly higher level of Aggrecan in the urine immediately after exercise compared to the values after three hours of microdialysis (rest), whereas the NEx group showed no significant difference between T1 and T2 (*P < 0.05). CTX-II displayed no changes over time.

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