Nissen J B, Avrach W W, Hansen E S, Stengaard-Pedersen K, Kragballe K
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Br J Dermatol. 1998 Dec;139(6):1012-9. doi: 10.1046/j.1365-2133.1998.02557.x.
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.
阿片肽脑啡肽已被证明可调节炎症反应以及角质形成细胞的增殖和分化。此外，银屑病皮损中脑啡肽水平升高。本研究的目的是确定死海的自然阳光与盐水浴相结合对银屑病皮肤中甲硫氨酸脑啡肽（e.n.k.）水平的影响。10名患者在死海接受了4周的治疗，并在治疗前后获取了角膜刀活检样本。通过放射免疫分析法测量从活检样本中提取的脑啡肽量。在死海的治疗使银屑病完全临床清除，对皮损皮肤的免疫组织化学染色显示，治疗降低了表皮厚度/角化不全以及CD3和CD68阳性细胞的真皮浸润，尽管在10例患者中只有2例的CD3和CD68阳性细胞数量恢复正常。然而，平均脑啡肽水平仅略有下降（21%）。此外，在死海接受治疗后，非皮损性银屑病皮肤中的脑啡肽水平较高，免疫染色显示，在一些患者中，治疗诱导了轻度表皮增生以及CD3和CD68阳性细胞的真皮浸润。在表皮角质形成细胞和真皮浸润细胞的细胞质中均检测到脑啡肽样免疫反应性。为了确定在死海接受治疗后皮肤中相对较高的脑啡肽水平是否由紫外线（UV）辐射引起，正常志愿者接受了单次剂量的UVA和UVB（2个最小红斑剂量）照射。UVA照射而非UVB照射使受照射皮肤中的平均脑啡肽水平提高了约6倍。此外，多次全身UVA照射不仅导致皮肤中脑啡肽水平升高，还导致血浆水平升高。总之，自然阳光与盐水浴相结合清除了银屑病，而未导致皮损脑啡肽水平显著下降。此外，非皮损脑啡肽水平升高。这些发现可能是UVA照射对皮肤中脑啡肽形成的直接刺激作用的结果。紫外线暴露后循环中脑啡肽水平升高可能有助于UVA照射的有益效果。
