The long term goal of the proposed project is to elucidate the role of intestinal immune system in modulating the activity of the enteric nervous system in inflammatory bowel disease (IBD) in our aging population. There is much evidence which indicates functional decline in systemic immune responses with aging. However there is no clear evidence suggesting specific effects of aging on gastrointestinal associated immune system and enteric nervous system. The fact that gastrointestinal tract is the largest immune organ in the body, has been ignored and much less attention has been given to the role of lamina propria T cells and intraepithelial lymphocytes (IEL), and antibody producing B cells. The changes may be related to quantitative and qualitative release of cytokines and inflammatory mediators and their interaction with secretory neurons within the wall of the gut. With the use of Lewis rat colitis model (chemical induction), we will pursue the following specific aims: 1) To ascertain if colonic tissues from rats have altered neurosecretory responsiveness associated with age during experimental colitis; 2) To ascertain the immunohistological distribution pattern, quantitation and phenotypic localization of T and B cells in intestinal compartment of Lewis rats of various age groups; 3) To isolate and ascertain the activity of isolated intestinal T cells to proliferate by in vitro proliferative assay; 4) To analyze cytokine profiles of the immune T cells such as IL-1, IL-2, IL- 4, IL-6, IL-8, IFN-gamma among others which accompany the induction of inflammatory response in-he gut; 5) To study the histological and ultra structural changes within the intestine during inflammatory phase in different age groups. The results of this study will contribute significantly to our knowledge of neuroimmune interactions and their role in IBD in aging rats. It will also provide insight into etiology, pathogenesis and strategies for management and basis for future development and selection of therapeutic measures for different age groups for intestinal inflammatory conditions.
