Kallikrein cascade and cytokines in inflamed joints

Rheumatoid arthritis is a chronic multi-system disease of unknown aetiology. The current hypothesis is that an unknown antigen triggers an autoimmune response in a genetically susceptible individual. The predominant pathological change is that of an inflammatory synovitis, characterised by cellular infiltrates and angiogenesis, with subsequent bone and cartilage destruction. These pathological changes are as a result of the activation of a variety of cells, inflammatory mediators, and effector molecules. The pro-inflammatory kinins and cytokines appear to play a central role in the pathogenesis of rheumatoid arthritis. Sufficient evidence exists that establishes a key role for the kallikrein-kinin cascade in inflamed joints. In addition, there appears to be an inter-relationship between cytokines and kinins in the inflammatory process. Kinins induce the release of cytokines, and cytokines have been shown to augment the effects of kinins. This may lead to an enhancement and perpetuation of the inflammatory process. In this review, we report a first study, correlating markers of disease with the kallikrein-kinin cascade and with cytokines.