Signal Transduction Pathways in Chronic Inflammatory Rheumatic Diseases

The rheumatic diseases have become a test bed for new therapies in chronic inflammatory immune-mediated diseases – and rightly so. The inflammatory response is relatively easy to quantify, and validated outcome measures are available that permit investigation of efficacy over short periods of time. The late 1990s and early 2000s heralded the era of biological therapy, pioneered in diseases such as rheumatoid arthritis; clinical trials in inflammatory bowel disease and psoriasis followed soon after. These breakthroughs in medicine confirmed unambiguously that it was possible to suppress inflammation in vivo with highly specific, targeted therapy – in this case monoclonal antibodies or derivatives thereof. In the context of cytokine blockade it put to bed the notion that there was redundancy of cytokine cascades, implying that there were hierarchies, and that interfering with expression of inflammatory mediators at a proximal/early level was a rational approach to reduce the burden of these chronic disabling diseases.