Elevation of interleukin 1 receptor antagonist in the stratum corneum of sun-exposed and ultraviolet B-irradiated human skin.

Keratinocytes produce not only interleukin 1 (IL-1) but also IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1. Because little is known about the presence of IL-1ra in the stratum corneum, we examined the content of IL-1ra in the stratum corneum, especially the balance between IL-1 and IL-1ra. IL-1 alpha and IL-1ra, but not IL-1 beta, were detected in the tape-stripped stratum corneum of healthy volunteers by enzyme-linked immunosorbent assays. IL-1 alpha and IL-1ra were bioactive as determined by thymocyte co-stimulation assay, and their molecular masses were 17 and 20 kDa, respectively, suggesting that the stratum corneum contains active forms of IL-1 alpha and IL-1ra produced by keratinocytes. The stratum corneum of an unexposed area, the inner side of the upper arm. contained more IL-1 alpha than a sun-exposed area, the face. In contrast, the stratum corneum of the sun-exposed area contained a markedly higher amount of IL-1ra than that of the unexposed area. The ratio of IL-1ra to IL-1 alpha was 8 in the unexposed area, and over 100 in the sun-exposed area. Therefore, IL-1 alpha activity was dominant in the unexposed area, and in contrast, IL-1ra activity was dominant in the sun-exposed area. An elevated level of IL-1ra was detected in the stratum corneum of the sun-exposed area independently of age. In the unexposed area, however, IL-1a increased, but IL-1ra decreased, with age, resulting in a significant decline of the ratio of IL-1ra to IL-1a with increasing age. Irradiation of 2 MED of ultraviolet B to the back skin, an unexposed area, resulted in striking elevation of IL-1ra in the stratum corneum in desquamating scales. These data suggest that IL-1ra in the epidermis may be inducible by chronic UV irradiation, although IL-1ra production in the epidermis may decrease with aging in the absence of any stimulus. IL-1ra in the epidermis may play a role in the regulation of IL-1-induced inflammatory responses, and an appropriate balance between IL-1 and IL-1ra may help to maintain homeostasis of the skin.