Nitric Oxide Appears to Be a Mediator of Solar-Simulated Ultraviolet Radiation-Induced Immunosuppression in Humans

Topical application of NG-methyl-L-arginine and 2,2′-dipyridyl were used to examine the respective roles of nitric oxide and reactive oxygen species in solar-simulated ultraviolet radiation-induced immunosuppression in humans in vivo. Immunosuppression was studied using a nickel contact hypersensitivity recall model. Ultraviolet radiation dose–responses were generated to determine the extent to which NG-methyl-L-arginine and 2,2′-dipyridyl affected the immune response. NG-methyl-L-arginine but not 2,2′-dipyridyl protected the immune system from ultraviolet radiation-induced suppression. Both NG-methyl-L-arginine and 2,2′-dipyridyl inhibited nitrite production. Nitrite is a degradation product of peroxynitrite, a cytotoxic mediator resulting from reactions between nitric oxide and reactive oxygen species. This suggests that nitric oxide, not its downstream product peroxynitrite, was likely to be responsible for solar-simulated ultraviolet radiation-induced immunosuppression. In contrast, both nitric oxide and reactive oxygen species were mediators of solar-simulated ultraviolet radiation-induced apoptosis and loss of dendritic S-100+ cells (probably Langerhans cells) from the epidermis. It is likely that different mechanisms are involved in these ultraviolet-induced endpoints and that events in addition to Langerhans cell depletion are important for local immune suppression to recall antigens in humans. Understanding the mechanisms of cutaneous ultraviolet-induced oxidative stress will assist in the future design of novel products that protect skin from photoaging and skin cancer