INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) STIMULATES REGROWTH OF THE DAMAGED INTESTINE IN RATS, WHEN ADMINISTERED FOLLOWING, BUT NOT CONCURRENT WITH, METHOTREXATE

Background: We tested the ability of insulin-like growth factor-I (IGF -I) to reduce damage to the intestinal mucosa (mucositis) in rats inje cted with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withd rawal of methotrexate. Methods: Rats were injected with methotrexate a t the start of days 1, 2 and 3. IGF-I was infused for 5 days, commenci ng at the start of day 1 [concurrent administration] or at the start o f day 4 [post-methotrexate administration]. Results: IGF-I administere d coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered post methotrexate stim ulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus h eight and ileal crypt depth respectively. Conclusions: Following intes tinal damage by methotrexate, IGF-I primarily induced growth of the di stal small intestine, The ineffectivenesss of concurrently administere d IGF-I may have represented an IGF-I-induced recruitment of prolifera ting epithelial cells to the anti-proliferative effects of methotrexat e.