title: High-concentration all-trans retinoic acid induces dermal inflammation and reduces the accumulation of type I procollagen in human skin in vivo.
abstract: BACKGROUND
  Because inflammation is a factor promoting ageing, all-trans retinoic acid (RA)-induced irritation may have a negative influence on collagen accumulation in human skin despite its stimulation of collagen production.
  
  
  OBJECTIVE
  To determine whether RA-induced irritation detrimentally affects RA efficacy as represented by new collagen synthesis.
  
  
  METHODS
  Retinoic acid (0·01%, 0·025% or 0·05%) or vehicle was applied to the buttock skin of elderly male volunteers three times a week for 8 weeks under continuous occlusion. Every 2 weeks, biopsy specimens were obtained and immunohistochemical analysis was performed to determine levels of type I procollagen expression and inflammatory cell infiltration.
  
  
  RESULTS
  Topical RA regardless of concentration increased type I procollagen expression in human skin in vivo after 2 weeks. However, only 0·01% RA continuously increased type I procollagen expression up to 8 weeks. After 4 weeks, significant infiltrations of macrophages and neutrophils were observed in 0·025% and 0·05% RA-treated skin, and procollagen expression had returned to baseline.
  
  
  CONCLUSIONS
  Excessive RA-induced inflammation might prevent collagen accumulation in aged skin despite the positive effect of RA on collagen production.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Yoon
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000187:drug effects; D012867:Skin / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D024042:Collagen Type I; D014212:Tretinoin