Ultraviolet-B-induced
erythema (one, two, or four times the minimal
erythema dose) was reduced but not abolished by application of 1%
indomethacin gel immediately after irradiation of human skin. Continuous synthesis of
prostaglandins is reflected by similar levels of
indomethacin-mediated inhibition of
erythema at any time within 48 h after irradiation. Repeated applications of
indomethacin did not increase the inhibition. Twenty-four hours after irradiation with four minimal
erythema doses, mean
prostaglandin E2 levels in suction
blisters were 27.2 ng per ml (SEM 11) compared with 8.6 ng per ml in unirradiated skin (n = 25; p < 0.01). Prosta glandin E2 levels in dermal 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 contribution to ultraviolet-B-induced
erythema. Ultraviolet
erythema was inhibited by
L-NAME in a dose-related fashion with 2 mM
L-NAME causing total abolition 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 suction
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 concentration of
prostaglandin E2. These findings confirm
prostaglandin E2 and NO to be mediators of ultraviolet-induced
erythema. They also show that there is prolonged synthesis of both mediators within the erythemal response and that synthesis of NO is induced by lower doses of ultraviolet B compared with that of
prostaglandin E2.