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

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. Objectives 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.