Does the response of the intestinal epithelium to keratinocyte growth factor vary according to the method of administration?

Background: Keratinocyte growth factor (KGF) is a potent mitogen and may be of value for the treatment of conditions such as short bowel syndrome and chemotherapy-induced mucositis. However the most efficacious route and meth od of administration is unclear. Methods: Rats maintained by total parenter al nutrition (TPN) were given KGF (1 mg/kg/rat/day, iv) infused continuousl y or as a once-daily injection. The same dose was also given sc. to chow-fe d rats. Changes in gut growth were assessed by measurement of wet weight, p roliferation (vincristine induced metaphase arrest) and crypt branching ind ex. Changes in gut hormone profile were also determined to examine if any t rophic effects were mediated via this mechanism. Results: KGF caused a 70-1 00% increase in wet weight of the stomach, small and large intestine of TPN -fed rats (P < 0.01) with no significant differences seen between the two m ethods of administration. The increase in metaphase counts was greatest in the stomach (about seven-fold P < 0.01), but was less pronounced in the dis tal small intestine and colon (about 50% increase). The trophic effect of K GF was much less prominent in orally-fed rats. Crypt branching index was si gnificantly reduced by KGF in the proximal small intestine of TPN, but not orally-fed rats. Plasma gastrin, PYY, total glucagon, enteroglucagon and GL P-1 all increased by two-three-fold tall P <0.01) in response to KGF wherea s insulin levels fell by about 25% in the TPN group. Conclusions: The mitog enic action of KGF occurred predominantly in the stomach and proximal small intestine. Its efficacy was less pronounced in orally-fed animals, suggest ing KGF may be of greatest benefit in conditions associated with lowered in testinal proliferation. Clinical trials of KGF can probably use single dail y iv injections without reduction in efficacy. (C) 2000 Elsevier Science BN . All rights reserved.