Contemporary concepts of inflammation, damage and repair in rheumatic diseases.

Chronic arthritis has been regarded as a disease resulting from a disequilibrium in pro- and anti-inflammatory cytokines. Restoration of this imbalance by using blocking antibodies or soluble receptors against a variety of inflammatory components has been the focus of most therapeutic interventions so far. More recently, other destructive mechanisms partially independent of inflammation have been elucidated, including osteoclast mediated bone resorption driven by the RANKL/RANK system. Despite efficient control of inflammation and destruction, little joint tissue repair has been observed. In addition, abnormal tissue responses such as cartilage calcification and ankylosis may contribute to disease progression and loss of joint function. We propose that 'true' disease remission may only be achieved with appropriate activation of local joint tissue responses leading to restoration of joint homeostasis and recovery of joint function. Understanding the molecular networks of joint homeostasis, repair and remodelling will be required to achieve this goal. Defining and validating clinical outcomes evaluating remission remain a challenge.