ABSTRACT
The gastrointestinal tract serves as a barrier between the host and the vast array of foreign antigen that is contained within its lumen. The mucosal immune system must balance two opposing functions; to mount an immune response to pathogens, whilst maintain ing tolerance to antigens derived from commensal bacteria and food. This balance is regulated by both cellular interactions and the release of soluble mediators such as cytokines. Diseases such as Crohn’s disease are characterized by alterations in the balance of pro-inflammatory and regulatory cytokines. There is considerable interest in therapeutic strategies that manipulate the cytokine balance within the mucosa. The cytokine interleukin-10 (IL-10) plays a pivotal role within the mucosal immune system impacting on both cell mediated and innate immune responses whilst promoting regulatory lymphocyte function. This role is highlighted both by the chronic ileocolitis that develops in gene targeted IL-10 knockout mice, and by the thera peutic efficacy of IL-10 injection in several animal models of colitis. However, trials of daily systemic IL-10 administration in patients with Crohn’s disease have reported only a modest clinical response. There is increasing evidence that focused IL-10 delivery using gene therapy strategies may enhance the therapeutic effect of IL-10 in intestinal inflammation.
