Differential Protection by Two Sunscreens from UV Radiation–Induced Immunosuppression

A controversy has arisen concerning the ability of sunscreens to protect mice from the immunosuppressive effects of UV radiation. We have assessed the photoprotection in hairless mice of two sun protection factor (SPF) 15 sunscreens containing different UVB (280-320-nm) absorbers, namely, octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethyl-hexyl-p-methoxycinnamate (2-EHMC). Following three minimum erythemal exposures to UV radiation, both systemic suppression of contact hypersensitivity to 2, 4-dinitrofluorobenzene and inductin of susceptibility to transplanted UV radiation-induced tumor cells was established. Topically applied 2-EHMC sunscreen protected totally From both forms of immunosuppression, but the o-PABA sunscreen failed to protect, although both sunscreens were equally effective in protection from UV radiation-induced erythema and edema

Isoflavonoid photoprotection in mouse and human skin is dependent on metallothionein

Previous studies report that selected topical isoflavonoids are immunoprotective in both mice and humans, when applied following UV irradiation. Isoflavonoids have documented antioxidant activity, but their mechanism of immunomodulation remains unclear. This study examines whether photoimmunoprotection by the isoflavonoids might result from their interaction with one cutaneous antioxidant known to modulate UV photodamage, metallothionein (MT). In mice bearing a null mutation for MT-I and -II, we found that immunoprotection by the isoflavonoid 4′,7-dihydroxyisoflavane (equol) against solar-simulated UV radiation (SSUV) or exogenous cis-urocanic acid was abrogated. Topical equol did not activate MT expression in normal mouse skin, but markedly enhanced the increase in MT expression in murine epidermis following SSUV irradiation. Normal human skin, unlike murine, expressed MT in the basal epidermis. Following SSUV irradiation, topical application of the related synthetic isoflavonoid NV-07α to human skin also markedly enhanced epidermal MT expression. The NV-07α has been reported previously to protect humans against the UV suppression of Mantoux reactions. Thus, epidermal MT expression appears to protect against photoimmunosuppression in both human and mouse skin. We speculate that equol and its related derivative NV-07α may activate the MT gene synergistically with SSUV, to produce the enhanced immunoprotective effect