Insulin-like growth factor-I reverses the impairment of wound healing induced by corticosteroids in rats

Abstract

Corticosteroids are widely used therapeutic agents that have as a major side-effect the impairment of wound healing. Two hypotheses were tested: 1) that antiinflammatory corticosteroids decrease the local insulin-like growth factor-I (IGF-I) response to injury; and 2) that locally administered IGF-I would overcome methylprednisolone-mediated suppression of healing. The IGF-I concentration was measured in fluid from wire mesh cylinder wounds in rats given saline or methylprednisolone im. Rats receiving 8 and 16 mg had decreased wound IGF-I levels of 32% and 56%, respectively, compared to the saline-injected controls. IGF-I was infused (15 micrograms/day) by osmotic minipumps into wire mesh cylinder wound chambers of methylprednisolone (8 mg)-treated rats for 7 and 14 days. Methylprednisolone decreased wound DNA to 21%, hydroxyproline to 30%, and total protein to 5% of the values found in saline-infused controls. A 14-day treatment with IGF-I completely reversed the effect of methylprednisolone and increased DNA, hydroxyproline, and total protein to 216%, 109%, and 96% of saline control values, respectively. In conclusion, corticosteroids depressed wound IGF-I concentrations in rats, and an infusion of IGF-I into wound chambers reversed the corticosteroid-induced impairment of wound healing, as determined by the DNA, hydroxyproline, and total protein contents in wound chambers.