Barr R M, Walker S L, Tsang W, Harrison G I, Ettehadi P, Greaves M W, Young A R
St John's Institute of Dermatology, Guy's, King's, and St Thomas' School of Medicine, King's College London, St Thomas' Hospital, London, UK.
J Invest Dermatol. 1999 May;112(5):692-8. doi: 10.1046/j.1523-1747.1999.00570.x.
Cytokines induced in skin by ultraviolet radiation cause local and systemic immunosuppression. Tumor necrosis factor alpha, interleukin-1, and interleukin-10 are key mediators in the mouse, but less is known about cytokine synthesis and function in ultraviolet-irradiated human skin. We exposed human skin to 3 minimal erythema doses of solar-simulated radiation and raised suction blisters at intervals to 72 h. Alloantigen presentation was suppressed in a mixed epidermal cell-lymphocyte reaction by 69% from 4 to 15 h post-solar-simulated radiation, but recovered to control values by 24 h. Tumor necrosis factor alpha was raised at 4 h after solar-simulated radiation, reached a maximum 8-fold increase at 15 h, then rapidly declined to control values. Interleukin-1alpha and interleukin-1beta were first increased at 15 h, and remained raised to 72 h, although interleukin-1beta declined from its 15 h maximum. Interleukin-10 increased a maximum 2-fold between 15 and 24 h, coincident with recovery of mixed epidermal cell-lymphocyte reaction responses and downregulation of tumor necrosis factor alpha and interleukin-1beta. Solar-simulated radiation differentially affected soluble tumor necrosis factor alpha receptors; soluble tumor necrosis factor-RI was suppressed 33% at 8-15 h whereas soluble tumor necrosis factor-RII increased 2-fold from 15 to 48 h. Interleukin-1 receptor antagonist was raised at all times post-irradiation. Interleukin-12 was not detectable in control or irradiated skin. These kinetics suggest the tumor necrosis factor alpha network has primary importance in ultraviolet-damaged human skin. The small increase in interleukin-10 implies that 3 minimal erythema doses of solar-simulated radiation is the threshold dose for its induction and local, rather than systemic, functions for interleukin-10 in immunosuppression and regulation of other cytokines.
紫外线辐射诱导皮肤产生的细胞因子会导致局部和全身免疫抑制。肿瘤坏死因子α、白细胞介素-1和白细胞介素-10是小鼠中的关键介质，但对于紫外线照射后的人类皮肤中细胞因子的合成和功能了解较少。我们将人类皮肤暴露于3个最小红斑量的模拟太阳辐射下，并每隔一段时间直至72小时产生抽吸水疱。在模拟太阳辐射后4至15小时，混合表皮细胞-淋巴细胞反应中的同种异体抗原呈递被抑制了69%，但在24小时时恢复到对照值。肿瘤坏死因子α在模拟太阳辐射后4小时升高，在15小时达到最大8倍的增加，然后迅速下降至对照值。白细胞介素-1α和白细胞介素-1β在15小时首次增加，并持续升高至72小时，尽管白细胞介素-1β从其15小时的最大值下降。白细胞介素-10在15至24小时之间最大增加2倍，这与混合表皮细胞-淋巴细胞反应的恢复以及肿瘤坏死因子α和白细胞介素-1β的下调同时发生。模拟太阳辐射对可溶性肿瘤坏死因子α受体有不同影响；可溶性肿瘤坏死因子-RI在8至15小时被抑制33%，而可溶性肿瘤坏死因子-RII在15至48小时增加2倍。白细胞介素-1受体拮抗剂在辐射后所有时间均升高。在对照或照射皮肤中未检测到白细胞介素-12。这些动力学表明肿瘤坏死因子α网络在紫外线损伤的人类皮肤中具有首要重要性。白细胞介素-10的小幅增加意味着3个最小红斑量的模拟太阳辐射是其诱导的阈值剂量，并且白细胞介素-10在免疫抑制和其他细胞因子调节中的功能是局部的而非全身的。
