Increased levels of enkephalin following natural sunlight (combined with salt water bathing at the Dead Sea) and ultraviolet A irradiation.

The opioid peptides enkephalins have been shown to modulate inflammatory responses and keratinocyte proliferation and differentiation. Furthermore, increased levels of enkephalin are present in psoriatic lesions. The purpose of the present study was to determine the effect of natural sunlight combined with salt water bathing in the Dead Sea on the methionine-enkephalin (e.n.k.) level in psoriatic skin. Ten patients were treated at the Dead Sea for 4 weeks, and keratotome biopsies were obtained before and after treatment. The amount of enkephalin extracted from the biopsies was measured by radioimmunoassay. Treatment at the Dead Sea resulted in a complete clinical clearance of psoriasis, and immunohistochemical stainings of lesional skin showed that the treatment decreased both epidermal thickness/parakeratosis and the dermal infiltration of CD3- and CD68-positive cells, although the number of CD3- and CD68-positive cells became normal in only two of the 10 cases. However, there was only a slight decrease in the mean enk levels (21%). Furthermore, the level of enk was high in non-lesional psoriatic skin after treatment at the Dead Sea, and immunostaining showed that, in some patients, the treatment induced a mild epidermal hyperplasia and a dermal infiltration of CD3- and CD68-positive cells. Enkephalin-like immunoreactivity was detected in the cytoplasm of both epidermal keratinocytes and dermal infiltrating cells. To determine whether the relatively high skin enk levels after treatment at the Dead Sea was caused by ultraviolet (UV) radiation, normal volunteers were exposed to a single dose of UVA and UVB (2 minimal erythema doses). UVA, but not UVB, irradiation stimulated the mean enk level in the irradiated skin by about sixfold. Furthermore, multiple whole-body UVA irradiations not only resulted in increased skin levels of enk, but also in increased plasma levels. In conclusion, natural sunlight combined with salt water bathing cleared psoriasis without causing a significant decrease in lesional enk levels. Furthermore, non-lesional enk levels were increased. These findings may be the result of a direct stimulatory effect of UVA irradiation on enk formation in the skin. It is possible that the increased circulating levels of enk after UV exposure may contribute to the beneficial effects of UVA irradiation.