The Pathogenesis of Mucosal Inflammation in Murine Models of Inflammatory Bowel Disease and Crohn Disease

doi:10.1059/0003-4819-128-10-199805150-00009

The Pathogenesis of Mucosal Inflammation in Murine Models of Inflammatory Bowel Disease and Crohn Disease

An edited summary of a Clinical Staff Conference held on 25 January 1997 at the National Institutes of Health, Bethesda, Maryland. Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:. “Fuss IJ. Cytokine production in Crohn disease, pp 849-851. In: Strober W, moderator. The pathogenesis of mucosal inflammation in murine models of inflammatory bowel disease and Crohn disease. Ann Intern Med. 1998; 128:848-856.”. Acknowledgments: The authors thank Drs. Rolf O. Ehrhardt, Markus F. Neurath, and Monica Boirivant for their vital role in this work and Nancy Shulman for editorial assistance. Requests for Reprints: Warren Strober, MD, Chief, Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N-238, Bethesda, MD 20892. Current Author Addresses: Drs. Strober, Ludviksson, and Fuss: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N-238, Bethesda, MD 20892.

Abstract

In recent years, it has become apparent that overproduction of the Th1 cytokines interleukin-12 and interferon-γ is the probable driving force behind murine models of intestinal inflammation resembling Crohn disease and intestinal inflammation in humans with Crohn disease. In addition, studies of murine models strongly suggest that this overproduction is associated with inadequate secretion of the counter-regulatory and anti-inflammatory cytokine transforming growth factor-β. Thus, mucosal inflammation in models (and possibly in humans) may result from an imbalance between normally occurring positive (immunogenic or inflammatory) responses and negative (tolerogenic or anti-inflammatory) mucosal immune responses. These new findings and the hypotheses that arise from them are being used to construct new approaches to the treatment of Crohn disease that are based on the administration of anti-inflammatory cytokines and anti-cytokine antibodies.