Modulation of gastrointestinal inflammation by chimeric proteins in experimental models

Conventional drug therapy in patients with chronic gastrointestinal inflamm ation is clinically effective in the majority of patients. However, in a re levant group of patients with highly active disease refractory to conventio nal drugs and for patients with severe side effects new therapeutic strateg ies are necessary. An advanced understanding of the immune mechanisms under lying chronic diseases resulted in the possibility to use chimeric proteins , in which the variable domains of an immunoglobulin are replaced by extrac ellular domains of cell surface molecules or cytokines for specific immunom odulation. The immunomodulating effects of chimeric proteins such as CTLA-4 -IgG, interleukin-10-IgG, IL-2-IgG or tumour necrosis factor (TNF)-receptor IgG have been proven beneficial in a variety of in vitro and in vivo model s of chronic gastrointestinal inflammation and autoimmune diseases. It thus seems likely that genetically engineered fusion proteins targeting specifi c elements of the immune response may become an essential element in new cl inical treatment protocols.