Regulation of experimental mucosal inflammation
Authors: Strober, Warren; Fuss, Ivan; Kitani, Atsushi
Source: Acta Odontologica Scandinavica, Volume 59, Number 4, 1 August 2001 , pp. 244-247(4)
Publisher: Informa Healthcare
Abstract:Studies conducted over the past 10 years have provided ample evidence that many types of inflammations arising from basic abnormalities of immune regulation are ultimately 'funneled' through a Th1 or Th2 T cell-mediated immune reaction. Thus, by understanding these types of reactions and, in particular, by identifying their natural checkpoints, one can control the inflammation regardless of its more basic causes. A case in point is the inflammatory disease of the intestine known as Crohn disease, a disease now thought to be due to one or more abnormalities leading to an excessive immune response to elements of the bacterial microflora of the gut. Both in murine models and by study of Crohn disease itself, we have shown that Crohn inflammation is due to a Th1 T-cell abnormality involving overproduction of interleukin (IL)12, interferon (IFN)-, and tumor necrosis factor (TNF)-α. In addition, we and others have shown that treatment of mice with anti-IL-12 or other agents that downregulate the level of IL-12 secretion can have a dramatic effect on the inflammation. This is because anti-IL-12 administration leads to apoptosis of activated Th1 T cells. A second checkpoint of Th1 T-cell-mediated inflammation involves its downregulation by the suppressor cytokine, transforming growth factor (TGF)-. We have been delivering TGF- to mice with experimental intestinal inflammation, using several novel approaches. In particular, we have successfully treated such mice with intranasally administered DNA encoding active TGF-. Another approach currently under investigation is delivery of TGF- by gene therapy. These and other developments in the understanding of inflammation paint a bright future for cytokine-based therapeutic agents. It is now apparent that these therapies are not only effective and safe but also potentially long-lasting.
Document Type: Research Article
Publication date: August 1, 2001