Targeting cytokines in autoimmunity: new approaches, new promise

The increasing understanding of the pathophysiology of a number of human autoimmune diseases, and the realisation that cytokines play a major role, has provided the pharmaceutical industry with a wide array of new targets for therapeutic intervention. This has also resulted in a surge of interest for the development of ways of blocking cytokines and their actions in a specific and safe manner. This article reviews the current status of anticytokine therapy and the major efficacy that anti-TNF-a monoclonal antibodies (mAbs) and soluble TNF receptors have demonstrated in the clinic, which has led to their approval for the treatment of rheumatoid arthritis (RA), Crohn's disease (CD), juvenile arthritis and psoriatic arthritis. In addition, the development of novel approaches of cytokine blockade that are based on the characterisation of intracellular signalling pathways regulating cytokine expression (e.g., nuclear factor kappa B [NF-kB] and p38 mitogen activated protein kinase [MAPK]) and the use of small molecule inhibitors are discussed. Whether these approaches will keep up with their early promise and become a major and widespread treatment for several devastating autoimmune diseases will depend on specificity, safety, durability of the benefit, and pharmacoeconomic issues.