Effects of steroids and retinoids on wound healing.
OBJECTIVE
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-beta (TGF-beta) and insulin-like growth factor-I (IGF-I) levels and tissue deposition in wounds and that retinoids stimulate corticosteroid-impaired TGF-beta and IGF-I release and collagen production.


METHODS
Randomized controlled trial.


METHODS
Wound healing research laboratory.


METHODS
Animal study.


METHODS
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.


METHODS
Hydroxyproline content was measured in the healing tissue 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 collagen deposition, TGF-beta and IGF-I levels over normal chow fed control animals (P<.05).


CONCLUSIONS
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.
Wicke
C
C
Department of Surgery, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany. Corinna.Wicke@med.uni-tuebingen.de
Halliday
B
B
Allen
D
D
Roche
N S
NS
Scheuenstuhl
H
H
Spencer
M M
MM
Roberts
A B
AB
Hunt
T K
TK
D000077556:Alitretinoin; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D016212:Transforming Growth Factor beta; D000077556:Alitretinoin; D000077555:Methylprednisolone Acetate; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D006909:Hydroxyproline; D008775:Methylprednisolone