Daniel H. Teitelbaum, MD
Professor, Department of Surgery
Director, Intestinal Failure Program
1500 East Medical Center Drive
Floor 3, Room 3970
Ann Arbor, MI 48109-5245
Total Parenteral Nutrition and Intestinal Immune Function
Our laboratory focuses on examining the local factors expressed by immunocytes (intraepithelial lymphocytes, IEL) which promote intestinal epithelial cell apoptosis and growth. We use two models: villus atrophy (parenteral nutrition) and villus growth (short bowel syndrome). Total parenteral nutrition (TPN), or the absence of enteral nutrition, is commonly used on a clinical basis. A major consequence of patients receiving TPN is a loss of systemic and particularly mucosal immune function. This can lead to an increased incidence of infectious complications. A long-standing project in our laboratory is to understand what mechanisms contribute to these complications. One potential source of organisms entering the host is via a loss of epithelial barrier function. We have shown that the use of TPN results in major changes in the mucosal immune populations; and that many of these changes result in epithelial cell proliferation, apoptosis and loss of barrier function.
Short bowel syndrome, or the lack of sufficient intestine to sustain life, is a devastating clinical problem in children and adults. A number of attempts have been made to manipulate the remaining bowel to promote adaptation, and increase absorptive function. Unfortunately, none of these have been uniformly successful, and many have a high associated morbidity. The goal of this project is to use distractive forces, applied in a linear direction, to promote bowel lengthening.
Inflammatory Bowel Disease
Our laboratory has found that the expression of angiotensin converting enzyme in the intestinal mucosa is highly correlated to epithelial cell apoptosis. Use of enalaprilat, an angiotensin converting enzyme inhibitor (ACE-I), can markedly down-regulate epithelial cell apoptosis, and decrease the local expression of tumor necrosis factor alpha (TNF-α).