Background Arthropathy is one of the major complications in hemophilia, leading to functional limitations and poor quality of life. Exercise is recommended as being beneficial for people with hemophilia to counteract the consequences of repetitive hemarthrosis, yet a lack of exercise-related evidence using exercise and control groups exists in this population.
Objectives To evaluate in an experimental model of blood-induced joint damage the effects of swimming exercise on systemic inflammatory parameters and pain behavior.
Methods The arthropathy was induced in Wistar rats by eight weekly intra-articular injections of 0.1 mL of autologous blood in their right knees, contra lateral knees were injected with the same amount of saline. Animals were divided into Control Group (C; n=8), Hemarthrosis (H; n=8), Hemarthrosis + Exercise (HE; n=10). HE group performed during 8 weeks a swimming protocol during 60 min/day (5 x week) with 5% body weight attached on their tails. Joint diameters were measured with a digital microcaliper and the difference (Δ) between both side were calculated post-study. Pain status was also assessed with a static weight-bearing incapacitance test (SWIT). Blood samples were collected before sacrifice and the serum levels of interleukins (IL-10, IL-1α, IL-6, IL-4, IL-17), tumor necrosis factor (TNF)-α, vascular endothelial grown factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were analyzed by Multiplex assay. Plasmatic Corticosteroid, ACTH and Melatonin hormones were also assessed.
Results When compared with H group, HE group presented reduced joint swelling (Δ=2.39cm vs. 0.66cm; p=0.0001) and pain (39.54 vs. 8.58% decrease weight-bearing in hemarthrosis side; p=0.002). As show in the figure below, hemarthrosis promoted an increase in the plasmatic level of IL1-α (H=10.9 pg/ml ±0.13 vs. HE=5.51 pg/ml ±0.46; p=0.039), TNF-α (H=5.08 pg/ml ±2 vs. HE=3.35 pg/ml ±1.78; p=0.031) and MCP-1 (H=639.86 pg/ml ±45.9 vs. HE 433.1 pg/ml ±10.7; p=0.033) and were reduced by swimming exercise protocol. The level of these plasmatic pro-inflammatory cytokines were also positively correlated with pain (IL1-α: p=0.039; TNF-α: p=0.013; MCP-1: p=0.014). A contrary effect was observed in the anti-inflammatory cytokine IL-4 (p=0,001) where it was reduced in hemarthrosis group (H=6,81pg/ml ±0.81) and was increased by the exercise protocol (HE=27.77 pg/ml ±4.8). Interestingly the pattern of Melatonin levels (H: 4.75 pg/ml ±1.4 vs. HE: 15.26 pg/ml ±5.4; p=0,049) was similar to IL-4.
Conclusions This is the first study showing the beneficial effects of swimming exercise inflammatory parameters of the blood-induced hemarthrosis in rats. Our data also showed the effectiveness of the exercise in controlling at the same time systemic cytokines and pain in the arthropathy. The most surprising finding of this study was swimming promoting melatonin liberation, which possibly act as an anti-inflammatory agent.
Acknowledgement FAPESP grant 12/18588–1
Disclosure of Interest None declared