Ultraviolet-B-induced erythema is mediated by nitric oxide and prostaglandin E-2 in combination

Ultraviolet-B-induced erythema (one, two, or four times the minimal erythem a dose) was reduced but not abolished by application of 1% indomethacin gel immediately after irradiation of human skin. Continuous synthesis of prost aglandins is reflected by similar levels of indomethacin-mediated inhibitio n of erythema at any time within 48 h after irradiation. Repeated applicati ons of indomethacin did not increase the inhibition. Twenty-four hours afte r irradiation with four minimal erythema doses, mean prostaglandin E-2 leve ls in suction blisters were 27.2 ng per nil (SEM 11) compared with 8.6 ng p er ml in unirradiated skin (n = 25; p < 0.01). Prostaglandin E2 levels in d ermal tissues, sampled by microdialysis (depth 0.6 +/- 0.1 mm), were 310 pg per ml (SEM 123) and 237 pg per ml (SEM 88) in irradiated and unirradiated skin, respectively (n = 7, n.s.). Nitric oxide also made a significant con tribution to ultraviolet-B-induced erythema. Ultraviolet erythema was inhib ited by L-NAME in a dose-related fashion with 2 mM L-NAME causing total abo lition of the response. L-NAME was effective at all time points up to 48 h suggesting that NO was produced continuously. NO was undetectable in suctio n blister fluid but in dermal microdialysate NO was present at 44.3 ng per ml (SEM 6.2) following ultraviolet B compared with 26.0 ng per ml (SEM 8.0) in unirradiated skin (p < 0.05), approximately 1000 times the molar concen tration of prostaglandin E-2. These findings confirm prostaglandin E-2 and NO to be mediators of ultraviolet-induced erythema. They also show that the re is prolonged synthesis of both mediators within the erythemal response a nd that synthesis of NO is induced by lower doses of ultraviolet B compared with that of prostaglandin E-2.