Insulin-like growth factor-I (IGF-I) Stimulates regrowth of the damaged intestine in rats, when administered following, but not concurrent with, methotrexate

Abstract

Background: We tested the ability of insulin-like growth factor-I (IGF-I) to reduce damage to the intestinal mucosa (mucositis) in rats injected with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withdrawal of methotrexate. Methods: Rats were injected with methotrexate at the start of days 1, 2 and 3. IGF-I was infused for 5 days, commencing at the start of day 1 [concurrent administration] or at the start of day 4 [post-methotrexate administration]. Results: IGF-I administered coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered postmethotrexate stimulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus height and ileal crypt depth respectively. Conclusions: Following intestinal damage by methotrexate, IGF-I primarily induced growth of the distal small intestine. The ineffectiveness of concurrently administered IGF-I may have represented an IGF-I-induced recruitment of proliferating epithelial cells to the anti-proliferative effects of methotrexate.

Key Words:

• IGF-I
• intestinal mucositis
• methotrexate
• rats