Cytokines in osteoarthritis: mediators or markers of joint destruction?

The integrity of articular cartilage is maintained by the balance between cytokine-driven anabolic and catabolic processes. Unregulated or excess influences of these molecules are thought to play a part in the pathophysiology of many joint diseases. However, the role of cytokines in osteoarthritis (OA) is not well established. Our aims are twofold: firstly to consider the evidence for the contribution of cytokines to the pathophysiology of OA and secondly to evaluate their potential as markers of disease activity in OA.

Cytokine homeostasis, the role of catabolic and anabolic cytokines in maintaining cartilage integrity, and the contribution of such cytokines to destructive processes in OA were examined. Consideration was given to the interrelationship between cartilage, bone, and synovium in OA; metabolites produced by such structures were compared with cytokines as indicators of disease activity.

The evidence reviewed suggests that interleukin-1 (IL-1) and the less potent tumor necrosis factor alpha (TNF alpha) are mediators of joint damage in OA. The cytokines interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) were implicted in both destructive and protective mechanisms, suggesting a dual role. Metabolites of the different components of the joint provided a better measure of disease activity than cytokines.

Experimental evidence is emerging that catabolic cytokines are mediators of joint damage in OA, although their usefulness as markers of disease activity is limited because of the need to monitor a wide range of ligands and their inhibitors simultaneously. In contrast, metabolites released from cells within bone, synovium, and cartilage related to disease activity and provided prognostic information.