W. Strober et al., THE PATHOGENESIS OF MUCOSAL INFLAMMATION IN MURINE MODELS OF INFLAMMATORY BOWEL-DISEASE AND CROHN-DISEASE, Annals of internal medicine, 128(10), 1998, pp. 848-856
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.