Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 21, 2006; 12(35): 5606-5610
Published online Sep 21, 2006. doi: 10.3748/wjg.v12.i35.5606
Interleukin-12 and Th1 immune response in Crohn’s disease: Pathogenetic relevance and therapeutic inplication
Ilaria Peluso, Francesco Pallone, Giovanni Monteleone
Ilaria Peluso, Francesco Pallone, Giovanni Monteleone, Dipartimento di Medicina Interna, Università Tor Vergata, Rome, Italy
Author contributions: All authors contributed equally to the work.
Correspondence to: Giovanni Monteleone, Dipartimento di Medicina Interna, Università Tor Vergata, Via Montpellier, 1, Rome 00133, Italy. gi.monteleone@med.uniroma2.it
Telephone: +39-6-72596158 Fax: +39-6-72596391
Received: June 14, 2006
Revised: July 15, 2006
Accepted: July 20, 2006
Published online: September 21, 2006

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL-12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.

Keywords: Interleukin-12, Type 1 helper T-cell cytokines, Inflammatory bowel disease