Exercise-induced changes in interleukin-10 in patients with knee osteoarthritis: new perspectives?

Osteoarthritis (OA) of the knee is a common chronic disease leading to increased morbidity and reduced quality of life. Although exercise therapy has been shown to be beneficial for both pain and physical functioning, its underlying mechanism is not fully understood. However, a recent study found an exercise-induced increase in interleukin-10 levels, to which anti-inflammatory and chondroprotective properties are ascribed, in the (peri-)synovial fluid of patients with knee OA. These interesting results provide more insight into the effects of exercise in OA and need to be validated and confirmed. Hopefully, the study offers a promising basis for further research

been shown to be benefi cial for pain and physical functioning. However, the underlying mechanism of the eff ects of exercise therapy has not been fully elucidated.
From that perspective, we welcome the article by Helmark and colleagues [1] in this issue of Arthritis Research & Th erapy. In the article, which shows that exercise therapy appears to infl uence the intra-articular infl ammatory response, the authors observed the eff ects of exercise on (peri-)synovial biochemical markers by using the microdialysis method. Surprisingly, this study showed that exercise might also infl uence the infl ammatory processes in the joint. Women with symptomatic knee OA and a Kellgren-Lawrence grade of at least 1 (n = 31) were randomly assigned to nonexercise or exercise therapy. Directly after exercise, blood and urine samples were taken and microdialysis catheters were placed. Th e catheters were positioned intra-articularly and extra-articularly (near the synovium), and every 30 minutes, samples were collected over a period of 3 hours. Th e intra-articular and peri-synovial interleukin-10 (IL-10) levels were signifi cantly increased after exercise, whereas no changes were found in IL-10 levels in the nonexercise group. Levels of IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) were signifi cantly increased in both groups.
Elevated levels of several cytokines, such as IL-6, IL-1, and TNF-α, are found in early and advanced OA [2]. Low-grade infl ammation has been implicated in the pathogenesis of OA, and synovitis is suggested to predict progression [3,4]. In line with this, there are several experimental studies that showed that neutralizing the infl ammatory response resulted in prevention of both chondrocyte apoptosis and cartilage degradation [5,6]. Increased levels of IL-10 have been identifi ed earlier in synovial fl uid of patients with OA [2]. However, the changes that exercise brought about in IL-10 levels, as shown in this study [1], are novel and interesting fi ndings.
Exercise has been shown to protect against cartilage loss in animal studies [7], and recently exercise therapy Abstract Osteoarthritis (OA) of the knee is a common chronic disease leading to increased morbidity and reduced quality of life. Although exercise therapy has been shown to be benefi cial for both pain and physical functioning, its underlying mechanism is not fully understood. However, a recent study found an exercise-induced increase in interleukin-10 levels, to which anti-infl ammatory and chondroprotective properties are ascribed, in the (peri-)synovial fl uid of patients with knee OA. These interesting results provide more insight into the eff ects of exercise in OA and need to be validated and confi rmed. Hopefully, the study off ers a promising basis for further research. has also been shown to infl uence human cartilage proper ties [8,9]. For example, shortly after exercise, an elevation of serum levels of cartilage oligomeric matrix protein (COMP) was found in patients with OA, suggesting an eff ect on cartilage metabolism [8]. Th ese interesting new results allow speculation that exercise therapy might have direct eff ects on cartilage homeostasis by aff ecting the intra-articular cytokine levels [1]. Th e anti-infl ammatory and the recently shown antiapoptotic eff ects of IL-10 on chondrocytes suggest that IL-10 might have chondroprotective activities [10]. However, minimal evidence of alterations in cartilage markers could be found in this study. Intra-articular COMP decreased instantly after exercise (P <0.05), but no changes in other cartilage degradation markers, such as COMP serum levels or CTX-II (type II collagen) urine levels, were found; such changes would have made the evidence stronger. It should be noted that owing to the technique, the authors were limited in the amount of synovial material available, and it was not possible to investigate more markers. Why there were no signifi cant changes in serum levels is not fully clear, but that might be related to the fact that serum levels refl ect cartilage damage of all joints.
Th e observation of increased intra-articular IL-10 levels after exercise therapy could lead to a greater understanding of the role of exercise in knee OA. Relevant new research questions arise: Why is IL-10 upregulated after exercise? Could the increase in IL-10 and decrease in COMP be confi rmed in com parable studies? What is the evidence for a causal relationship of IL-10 and COMP, or are the changes coincidences? Why is COMP, but none of the other cartilage degradation markers, decreased?
Given the paucity of eff ective treatment strategies in OA, these observations hopefully will prompt further investigations on the infl uence of exercise and intraarticular IL-10 levels and cartilage degradation. Nevertheless, the fi rst step is that these data be validated and confi rmed by others.

Conclusions
Exercise therapy infl uences the intra-articular IL-10 levels in patients with knee OA. Th e pathophysiological mechanism underlying the eff ects of exercise therapy has not been fully elucidated. It has been suggested that exercise therapy results in cartilage degradation by aff ecting the low-grade infl ammatory state. Further research is required.