NUTRITIONAL AND INTESTINAL EFFECTS OF THE NOVEL IMMUNOSUPPRESSIVE AGENTS - DEOXYSPERGUALIN, RAPAMYCIN, AND MYCOPHENOLATE MOFETIL

Objectives: Transplantation of the small intestine would be an attract ive therapeutic option for treatment of short bowel syndrome if effect ive, nontoxic immunosuppressive agents could be developed. This study examines the effect of three newly developed immunosuppressive agents: rapamycin, deoxyspergualin, and mycophenolate mofetil, on the nutriti onal status and intestinal function of normal juvenile rats. Design & Methods: Rapamycin (2 mg/kg every second day), deoxyspergualin (2 mg/k g every second day) and mycophenolate mofetil (MM) (25 mg/kg every sec ond day) were injected subcutaneously for six weeks. Results: Rapamyci n and deoxyspergualin caused significant reductions in weight gain wit hout impairing feed intake. Both drugs caused small decreases in fat a bsorption; treatment with DSG induced an increase in permeability to T c-99-DTPA. However, the permeability to other markers, such as mannito l and lactulose, was decreased in the rapamycin and mycophenolate mofe til-treated animals. Intestinal function in vitro was quantified using glucose flux (absorption). In the rapamycin group, there was a signif icant decrease in ileal uptake of glucose, with the net flux (absorpti on) being zero; there was an associated loss of villous size histologi cally. In the deoxyspergualin-treated groups, there was a decrease in the jejunal glucose flux. In the mycophenolate mofetil-treated animals , there was a decrease in jejunal with a compensatory increase in ilea l glucose absorption. There were minor variations in intestinal morpho logy, but these were not consistent. Conclusions: Rapamycin and deoxys pergualin in these doses cause a significant reduction in weight gain in healthy juvenile animals, and all the drugs caused changes in the a ctive transport characteristics of the intestine. Accordingly, the use of these drugs for intestinal transplantation should be evaluated car efully for their nutritional impact.