Review article: the immunoregulatory cytokine interleukin-10 - a therapy for Crohn's disease?

The gastrointestinal tract serves as a barrier between the host and the vas t array of foreign antigens that are contained within its lumen. The mucosa l immune system must balance two opposing functions: to mount an immune res ponse to pathogens, whilst maintaining tolerance to antigens derived from c ommensal bacteria and food. This balance is regulated by both cellular inte ractions and the release of soluble mediators called cytokines. Diseases su ch as ulcerative colitis and Crohn's disease are characterized by alteratio ns in the balance of pro-inflammatory and regulatory cytokines. Interleukin-10 is a regulatory cytokine which inhibits both antigen present ation and subsequent pro-inflammatory cytokine release. In addition, there is evidence that it promotes the formation of antigen-specific regulatory T -cell clones. The pivotal role played by interleukin-10 within the mucosal immune system is demonstrated both by the chronic ileocolitis that develops in gene-targeted interleukin-10 knock-out mice, and by its therapeutic eff icacy in several animal models of colitis. However, trials of daily systemic interleukin-10 administration in patients with Crohn's disease have reported only a modest clinical response. Advanc es in the analysis of functional polymorphisms in the interleukin-10 gene m ay allow therapy to be targeted to patients who will respond. Finally, ther apeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response.