Review
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 7, 2006; 12(29): 4628-4635
Published online Aug 7, 2006. doi: 10.3748/wjg.v12.i29.4628
Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules
Naohiko Harada, Hirotada Akiho, Takahiro Mizutani, Kuniomi Honda, Kazuhiko Nakamura
Kazuhiko Nakamura, Kuniomi Honda, Takahiro Mizutani, Hirotada Akiho, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Naohiko Harada, Fukuoka-Higashi Medical Center, Koga 811-3195, Japan
Correspondence to: Naohiko Harada, MD, PhD, Fukuoka-Higashi Medical Center, 1-1-1, Chidori, Koga-city, Fukuoka 811-3195, Japan. haradan@fukuokae2.hosp.go.jp
Telephone: +81-92-9432331 Fax: +81-92-9438775
Received: October 3, 2005
Revised: October 28, 2005
Accepted: November 10, 2005
Published online: August 7, 2006
Abstract

The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-α monoclonal antibody, infliximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab. Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Anti-interferon-γ and anti-CD25 therapies were developed, but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach. Antibodies against α4 integrin and α4β7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 (ICAM-1) may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD.

Keywords: Inflammatory bowel disease; Cytokine; Adhesion molecule; Treatment