COMBINED INTESTINAL TREFOIL FACTOR AND EPIDERMAL GROWTH-FACTOR IS PROPHYLACTIC AGAINST INDOMETHACIN-INDUCED GASTRIC DAMAGE IN THE RAT

1. The availability of recombinant epidermal growth factor provides a potentially exciting development for the treatment of gastrointestinal ulceration. However, because of its potent mitogenic activity, there is a need for strategies which reduce the dose required. Intestinal tr efoil factor stimulates mucosal healing without increasing proliferati on. Studies were undertaken to examine the biological effects of rat i ntestinal trefoil factor and/or human epidermal growth factor upon gas trointestinal epithelial cell functions pertinent to mucosal protectio n, using two wounding models. 2. The study of epithelial restitution i n vitro demonstrated a marked synergistic effect on the rate of migrat ion of the wound edge when intestinal trefoil factor was used in combi nation with epidermal growth factor. There was no increased cellular p roliferation due to the addition of intestinal trefoil factor to the c ells when given alone, or to the stimulatory effect of cells treated w ith epidermal growth factor. In the rat model of gastric ulceration, t he presence of both epidermal growth factor and intestinal trefoil fac tor protected against the development of indomethacin-induced gastric lesions. 3. We conclude that combination therapy of epidermal growth f actor with intestinal trefoil factor could provide a more potent, safe r approach to the treatment of human gastrointestinal ulceration.