1. Intestinal atrophy contributes to the clinical difficulties of patients on parenteral nutrition. Systemic administration of epidermal growth factor reverses this effect, but there is concern over the clinical safety of intravenous administration of growth factors. We therefore investigated whether administration of luminal epidermal growth factor could reverse the atrophy induced in a rat model of parenteral nutrition when epidermal growth factor was given alone or in combination with soya bean trypsin inhibitor to reduce proteolytic digestion of the epidermal growth factor.
2. Infusion of soya bean trypsin inhibitor alone decreased intraluminal tryptic activity by about 90% but did not result in increased proliferation. Intragastric infusion of epidermal growth factor (72 μg/day per rat) caused a 26% increase in proliferation (determined by 2-h metaphase arrest) in the duodenum (P < 0.01) when compared with animals receiving ‘control’ intragastric infusion. However, intragastric epidermal growth factor had no effect on more distal regions of the bowel, probably reflecting rapid proteolysis of the epidermal growth factor by luminal proteases. In contrast, a trophic effect of luminal epidermal growth factor was seen in the duodenum (28% increase, P < 0.01) and jejunum (24% increase, P < 0.05) of animals which had received epidermal growth factor with soya bean trypsin inhibitor. This was probably due to the soya bean trypsin inhibitor decreasing the rate of degradation of epidermal growth factor by intestinal proteases, allowing biologically active epidermal growth factor to reach more distal portions of the bowel.
3. We conclude that luminal administration of epidermal growth factor in combination with protease inhibitors could provide a novel approach to the treatment of intestinal atrophy induced by parenteral nutrition. This approach may also be useful for the treatment of ulceration of the small intestine in conditions such as necrotizing enterocolitis or Crohn's disease. Clinical studies are recommended.
