THE PATHOGENESIS OF MUCOSAL INFLAMMATION IN MURINE MODELS OF INFLAMMATORY BOWEL-DISEASE AND CROHN-DISEASE

In recent years, it has become apparent that overproduction of the Th1 cytokines interleukin-12 and interferon-gamma is the probable driving force behind murine models of intestinal inflammation resembling Croh n disease and intestinal inflammation in humans with Crohn disease. In addition, studies of murine models strongly suggest that this overpro duction is associated with inadequate secretion of the counter-regulat ory and anti-inflammatory cytokine transforming growth factor-beta. Th us, 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-inflammator y) mucosal immune responses. These new findings and the hypotheses tha t arise from them are being used to construct new approaches to the tr eatment of Crohn disease that are based on the administration of anti- inflammatory cytokines and anticytokine antibodies.