Drug discovery and development for inflammatory diseases

Numerous recent investigations have pointed to a key role of the pro-inflammatory, pleotropic cytokines TNF-alpha and IL-1 in host defence and inflammatory disease processes. TNF and IL-1 overexpression has been found in disease target tissue and in the circulation of patients with acute and chronic inflammatory diseases, and it was suggested early on in this field of basic medical research that TNF-alpha and IL-1 were crucial in these diseases. Over the last 10 years, several approaches to inhibit TNF-alpha and, in one case, IL-1 activity, have been developed by the biotechnology and pharmaceutical industries. These include neutralising antibodies to TNF-alpha as well as soluble TNF-alpha receptors with characteristic properties designed to bind the 17 kDa soluble trimeric TNF-alpha and the 26 kDa membrane-bound form of TNF-alpha. Clinical trials have demonstrated significant effects with these agents and it is likely that blocking TNF-alpha will become an important standard therapeutic option for clinicians. The data available from these trials contribute to the further understanding of inflammation by demonstrating the major role of these cytokines. This research and clinical background have provided the basis for a variety of lectures on novel drug discovery targets, the current status of previously identified targets and technologies to develop new therapeutics in inflammation. At this meeting, emphasis was placed upon drug targets and their validation in animal models and early stage clinical trials.