Protection against UV-induced systemic immunosuppression in mice by a single topical application of the antioxidant vitamins C and E.
OBJECTIVE
Reactive oxygen species are involved in UV-induced suppression of the immune system. Topical treatment with the antioxidant vitamins C (L-ascorbic acid, ASC) and E (D-alpha-tocopherol, TOC) can support the endogenous antioxidant defence system and prevent immunosuppression.


METHODS
Mice were topically treated with a single dose of ASC, TOC or a combination and irradiated with UVB. Then systemic immunosuppression was measured using a model based on the induction of a contact hypersensitivity response to dinitrofluorobenzene. To investigate the mechanism of protection, cis-urocanic acid-induced immunosuppression was investigated in a different contact hypersensitivity model measuring local immunosuppression. The levels of ASC and TOC in the epidermis were determined by HPLC.


RESULTS
Both ASC and TOC prevented UV-induced suppression of the contact hypersensitivity response. TOC was effective at doses of 2.5 to 10 nmol/cm2 and ASC at 0.5 to 5 micromol/cm2. At the highest dose, the response in the ASC-treated mice was no longer significantly different from that in the positive control group. Contrary to expectations, combinations of the two compounds did not provide additional protection. The experiments with ASC or TOC against immunosuppression by cis-urocanic acid also yielded protection, but this was less efficient than against UV. The concentrations of ASC and TOC in the epidermis were so low that UVB absorption could be excluded as the cause of the protection.


CONCLUSIONS
ASC and TOC can be used to prevent systemic UV-induced immunosuppression. They are effective at relatively low doses after a single topical application prior to the irradiation.
Department of Medicinal Photochemistry, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands. steenvoo@chem.leidenuniv.nl
D P
DP
Steenvoorden
G
G
Beijersbergen van Henegouwen
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000032:analysis / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D007108:Immune Tolerance / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014560:Urocanic Acid / Q000633:toxicity; D014810:Vitamin E / Q000032:analysis / Q000494:pharmacology*
D000975:Antioxidants; D014810:Vitamin E; D014560:Urocanic Acid; D001205:Ascorbic Acid