Inflammatory bowel disease (IBD) is a collective term that includes Crohn's disease and ulcerative colitis. Although both disorders have a distinct clinical course with characteristic pathophysiology, the destructive and progressive course of IBD probably is due to persistent elevated expression of interleukin-1 (IL-1) by macrophages in the bowel of affected patients. IL-1, a central mediator of inflammation responsible for initiating a host of immunologic events, is a logical target for anti inflammatory therapies in IBD. Current drug therapies are directed at ameliorating the effects of IL-1. However, the therapies are not always effective and are associated with untoward side effects. The long term objective of this proposal is to develop an alternative therapy, oral formulations of recombinant adenoviral vectors containing the transgene for interleukin-1 receptor antagonist protein (IL-1ra). This vector is biologically active both in vitro and in vivo, and is capable of expressing therapeutic levels of IL-1ra. This initial phase will examine the efficiency and duration of IL-1ra gene expression following adenoviral mediated gene transfer to normal rat ileum.
