29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

Role of NO in UV Immunosuppression in Humans and Mice

Abstract-
We investigated whether NO or oxygen radicals are involved in UV immunosuppression in humans and mice using the inhibitors of nitric oxide and reactive oxygen production NG-monomethyl-L-arginine acetate (L-NMMA) and 2,2-dipyridyl respectively. Groups of 16 nickel-allergic human volunteers were recruited and irradiated with a range of doses of solar-simulated UV (ssUV) for 4 consecutive days with and without NO or reactive oxygen inhibition. Each skin site was then challenged with nickel and the ensuing contact sensitivity response assessed 72 h later by reflectance spectroscopy. A UV-induced dose response for suppression of this recall response was observed. L-NMMA but not dipyridyl protected this response from ssUV indicating that in humans NO but not iron-catalysed reactive oxygen is involved in immunosuppression. In contrast, studies in mice showed both L-NMMA and dipyridyl to prevent UVA-induced suppression of contact sensitivity. In further studies mice were protected with a sunscreen containing the UVB absorber 2-ethyl hexyl methoxycinnamate. Addition of these inhibitors to the sunscreen did not affect the sun protection factor (SPF), but lowered the level of oedema. Combination of both inhibitors with the sunscreen however increased the SPF from 5 to 5.5. The immune protection factor (IPF) of the sunscreen was only 1.18, but addition of neither dipyridyl nor L-NMMA singly or in combination measurably improved immune protection. However both inhibitors improved the ability of the sunscreen to prevent UV carcinogenesis. The results indicate that NO and oxygen radicals produced in response to UV radiation are important for erythema, immunosuppression and carcinogenesis, and addition of inhibitors improves the protective capacity of sunscreens.

Keywords: Nitric oxide, Immunosuppression, Sunscreens, Carcinogenesis