THE EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I ON WOUND-HEALING VARIABLESAND MACROPHAGES IN RATS

Objective: To assess the effect of insulin like growth factor I (IGF-I ) depletion and restoration on the number of wound macrophages and wou nd healing variables. Design: Fourteen-day, placebo-controlled trial. Setting: Animal research laboratory. Study Participants: Sham-operated and hypophysectomized healthy male rats weighing 300 g. Intervention: Random assignment to a 14-day IGF-I (10 mu g per wound per day) or pl acebo infusion directly into standardized Hunt-Schilling dorsal wound chambers. Main Outcome Measures: Wound healing variables (dry tissue w eight, total protein, DNA, and hydroxyproline content), and number and concentration of wound macrophages. Results: The IGF-I depletion in h ypophysectomized rats decreased wound protein, DNA, and hydroxyproline content of wounds by 50%, and IGF-I infusion returned these variables to near that of sham-operated rats. Wound macrophage concentrations d ecreased by 50% from control in the IGF-I depleted rats and increased to 75% of control with IGF-I infusion. Conclusion: Insulinlike growth factor I may have a fundamental role in wound healing and may exert pa rt of its stimulatory effect through macrophages. Although an independ ent effect of hypophysectomy on macrophages and collagen deposition is not excluded, we believe it is unlikely given the return to normal va lues with IGF-I infusion.