Effects of steroids and retinoids on wound healing

Hypothesis: Anti-inflammatory corticosteroids significantly impair wound he aling. Retinoids partially, but significantly, reverse this effect. Little is known about the mechanism of steroid retardation or retinoid reversal. W e hypothesized that corticosteroids lower transforming growth factor-beta ( TGF-beta) and insulinlike growth factor-I (IGF-I) levels and tissue deposit ion in wounds and that retinoids stimulate corticosteroid-impaired TGF-beta and ICF-I release and collagen production. Design: Randomized controlled trial. Setting: Wound healing research laboratory. Participants: Animal study. Interventions: 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 (D epo-Medrol). Two preparations of retinoids were used in separate experiment s: all-trans-retinoic acid and 9-cis-retinoic acid that were fed orally. Mule Outcome Measures: Hydroxyproline content was measured in the healing t issue and TGF-beta and IGF-I levels were analyzed in the wound fluid. Results: Methylprednisolone treatment significantly decreased TGF-beta 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-< beta> and IGF-I decrease and significantly increased hydroxyproline content toward normal levels (P<.05). Oral all-trans-retinoic acid enhanced collag en deposition, TGF-<beta> and IGF-I levels over normal chow fed control ani mals (P<.05). Conclusions: Steroids and retinoids have antagonistic effects on growth fac tors and collagen deposition in wound healing. These effects can be relevan t fur treatment options in a clinical setting.