Effects of ultraviolet radiation on the production of epidermal-derived thymocyte activating factor/interleukin-1

The effects of both a single exposure and multiple exposure to ultraviolet radiation (UVR) on the production and/or release of epidermal cell-derived thymocyte activating factor/interleukin-1 (ETAF/IL-1) were investigated. A single exposure to UVR enhances the release of ETAF/IL-1 both in vitro and in vivo. This conclusion was based on the observation that: (1) in vitro UV-irradiation of a keratinocyte cell line elevated the release of ETAF/IL-1 on a per cell basis; (2) exposure of animals to UVR stimulated a number of in vivo biologic responses which are known to be mediated by ETAF/IL-1; (3) ETAF/IL-1 could be detected in the serum of UVR exposed but not normal animals. Exposure of mice of UV-irradiation on a daily basis induced a "desensitized" state in which animals were found to be refractory to further stimulation with this inflammatory agents. A similar desensitization or "tolerance" was also shown to be induced by multiple intraperitoneal injections of bacterial lipopolysaccharide (LPS). Desensitization, induced by LPS or UVR, was found to be regulated at the site of interaction between the cells capable of ETAF/IL-1 production and the exogenous inflammatory stimulus. However, LPS-desensitization and UVR-desensitization are not regulated n the same manner. Peritoneal macrophages from LPS-desensitized mice demonstrated a reduced capacity to secrete ETAF/IL-1 in vitro, when compared to macrophages from normal animals, and were found to express this mediator on their cell surface. Membrane-associated forms of ETAF/IL-1 have not been demonstrated to be present on macrophages from normal animals. Therefore, macrophages appear to reduce their secretion of ETAF/IL-1 and increase the expression membrane associated forms of this mediator following daily stimulation with an inflammatory agent. In contrast, keratinocyte obtained from normal mice or the irradiated site of UVR desensitized animals both secrete ETAF/IL-1 and express membrane-associated forms of this mediator on their cell surface. These results indicate that the regulatory mechanisms for ETAF/IL-1 production which are employed by the Keratinocyte are distinct from those regulating ETAF/IL-1 production by macrophage.