Despite many beneficial effects on dermatological applications,
retinol and its derivatives cause severe local irritation manifested as mild
erythema and stratum corneum peeling of the skin. It is hypothesized that
cytokines may be important inflammatory mediators in
retinoid-induced
dermatitis. The present study was designed to determine
cytokine mediators and thereby, to screen potential anti-irritants in
retinoid-induced
inflammation. The changes in
mRNA expression of
inflammation-related
cytokines including mouse analogue of human
monocyte chemoattractant protein-1 (MCP-1) (JE), mouse analogue of human
interleukin-8 (IL-8) (KC),
tumor necrosis factor-alpha (
TNF-alpha),
interferon-gamma (IFN-gamma),
IL-12p40,
IL-6,
IL-10, Eotaxin were determined in mouse epidermal cells treated by 2%
retinol using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The up-regulated
mRNA level was confirmed with
protein levels in culture supernatants from human epidermal keratinocytes, melanocytes, and fibroblasts treated with 10 microM
retinol or
retinoic acid. As results,
retinoid-induced
inflammation was mainly mediated through MCP-1 and
IL-8 as evidenced by increased levels of
mRNA expression and
protein secretion. The potential anti-
irritant substances including
beta-sitosterol, Magnoliae flos, beta-
glycyrrhetinic acid, SC-
glucan, Ginko extract, Raspberry extract, Schisandra extract, Cola extract, Enna complex or Vegetol red grapevine extract were evaluated for their inhibitory effects on
retinol-induced
cytokine (MCP-1 and IL-8) secretion in vitro cultured human fibroblasts. Furthermore, in vivo efficacy tests for the
retinol-induced irritancy were performed using Draize skin irritation test in the rabbit and human patch test. Most of the substances that reduced the secretion of MCP-1 and
IL-8 in vitro cultured fibroblasts, showed a good inhibition against the
retinol-induced irritation in the rabbit and human patch test. In conclusion, the present study demonstrated that among proinflammatory
cytokines, MCP-1 and
IL-8 mainly mediated
retinol-induced skin irritation, and that inhibition of production of these
cytokines can be applied as good markers to screen the anti-irritants against the
retinol-induced irritation.