High-concentration all-trans retinoic acid induces dermal inflammation and reduces the accumulation of type I procollagen in human skin in vivo.

Abstract

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. To determine whether RA-induced irritation detrimentally affects RA efficacy as represented by new collagen synthesis. 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. 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. Excessive RA-induced inflammation might prevent collagen accumulation in aged skin despite the positive effect of RA on collagen production.