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 vast array of foreign antigens that are contained within its lumen. The mucosal immune system must balance two opposing functions: to mount an immune response to pathogens, whilst maintaining tolerance to antigens derived from commensal bacteria and food. This balance is regulated by both cellular interactions and the release of soluble mediators called cytokines. Diseases such as ulcerative colitis and Crohn's disease are characterized by alterations in the balance of pro-inflammatory and regulatory cytokines. Interleukin-10 is a regulatory cytokine which inhibits both antigen presentation 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 efficacy 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. Advances in the analysis of functional polymorphisms in the interleukin-10 gene may allow therapy to be targeted to patients who will respond. Finally, therapeutic strategies utilizing gene therapy may enhance mucosal delivery and increase therapeutic response.
Lindsay
J O
JO
Department of Gastroenterology, Imperial College School of Medicine, London, UK. j.lindsay@ic.ac.uk
Hodgson
H J
HJ
D002986:Clinical Trials as Topic; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015316:Genetic Therapy; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D018579:Patient Selection; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology
D016753:Interleukin-10