Anti-inflammatory corticosteroids significantly impair wound healing. Retinoids partially, but significantly, reverse this effect. Little is known about the mechanism of steroid retardation or retinoid reversal. We hypothesized that corticosteroids lower transforming growth factor-β (TGF-β) and insulin-like growth factor-I (IGF-I) levels and tissue deposition in wounds and that retinoids stimulate corticosteroid-impaired TGF-β and IGF-I release and collagen production.
Randomized controlled trial.
Wound healing research laboratory.
Four wire mesh wound cylinders were implanted subcutaneously into the backs of 72 male Sprague-Dawley rats. Wound healing was impaired by a single subcutaneous injection of 6 mg of methylprednisolone acetate (Depo-Medrol). Two preparations of retinoids were used in separate experiments: all-trans-retinoic acid and 9-cis-retinoic acid that were fed orally.
Main Outcome Measures
Hydroxyproline content was measured in the healing tissue and TGF-β and IGF-I levels were analyzed in the wound fluid.
Methylprednisolone treatment significantly decreased TGF-β and IGF-I levels in the wound fluid and hydroxyproline content in the tissue (P<.05). Oral all-trans- and 9-cis-retinoic acid partially reversed the TGF-β and IGF-I decrease and significantly increased hydroxyproline content toward normal levels (P<.05). Oral all-trans-retinoic acid enhanced collagen deposition, TGF-β and IGF-I levels over normal chow fed control animals (P<.05).
Steroids and retinoids have antagonistic effects on growth factors and collagen deposition in wound healing. These effects can be relevant for treatment options in a clinical setting.