Noonan F P, De Fabo E C
Department of Dermatology, George Washington University Medical Center, Washington, DC 20037.
Photochem Photobiol. 1990 Oct;52(4):801-10. doi: 10.1111/j.1751-1097.1990.tb08685.x.
Irradiation of mice with UVB suppresses contact hypersensitivity either "locally", i.e. when sensitizer is applied to the UV irradiated site, or "systemically", i.e. when sensitizer is applied to a site distal to the site of irradiation. It has been suggested that local suppression requires lower doses of UV than does systemic suppression, and that different mechanisms are therefore responsible. We undertook a detailed analysis of the dose-response and kinetics of UV-induced local and systemic suppression of contact hypersensitivity to trinitrochlorobenzene in two strains of mice, C57BL/6 and BALB/c. We found that the UV dose-responses for systemic and local suppression were identical within the same strain. Comparison, however, of UV dose-responses between strains indicated that C57BL/6 mice required 6.4 times less UV than did BALB/c mice to generate an equivalent amount of suppression. In both strains, local suppression was initiated if sensitizer was applied immediately, or 1 or 3 days after completion of a single dose of UV. In contrast, systemic suppression was initiated only if sensitizer was applied 3 days after UV irradiation. Thus local suppression was generated in the absence of significant systemic suppression (but not vice versa), and this was dependent on time of application of sensitizer after UV irradiation, not on the dose of UV administered. Filtration of the UV source with Mylar indicated that UVB was responsible for initiating both local and systemic suppression. In summary, these results indicate that (1) genetically determined differences in susceptibility to UV suppression exist, (2) the time courses of generation of local and systemic suppression are identical, and therefore use of the terms "low dose" and "high dose" to refer respectively to local and systemic suppression by UV irradiation are incorrect. We conclude that a common mechanism initiates UV-induced local and systemic suppression of contact hypersensitivity by the immediate formation, at the site of UV irradiation, of an immunosuppressive signal which takes between 1 and 3 days to act systemically.
用中波紫外线(UVB)照射小鼠会抑制接触性超敏反应,这种抑制作用可分为“局部”抑制,即当致敏剂应用于紫外线照射部位时;或“全身”抑制,即当致敏剂应用于照射部位远端时。有人提出,局部抑制所需的紫外线剂量低于全身抑制,因此两者的作用机制不同。我们对C57BL/6和BALB/c两种品系小鼠紫外线诱导的对三硝基氯苯接触性超敏反应的局部和全身抑制的剂量反应及动力学进行了详细分析。我们发现,同一品系内全身抑制和局部抑制的紫外线剂量反应是相同的。然而,不同品系之间紫外线剂量反应的比较表明,C57BL/6小鼠产生等量抑制所需的紫外线比BALB/c小鼠少6.4倍。在这两种品系中,如果在单次紫外线照射完成后立即、1天或3天应用致敏剂,均可引发局部抑制。相比之下,全身抑制仅在紫外线照射3天后应用致敏剂时才会引发。因此,局部抑制是在没有明显全身抑制的情况下产生的(反之则不然),这取决于紫外线照射后致敏剂的应用时间,而不是所给予的紫外线剂量。用聚酯薄膜过滤紫外线光源表明,UVB是引发局部和全身抑制的原因。总之,这些结果表明:(1)存在对紫外线抑制敏感性的遗传决定差异;(2)局部和全身抑制的产生时间进程相同,因此用“低剂量”和“高剂量”分别指代紫外线照射引起的局部和全身抑制是不正确的。我们得出结论,一种共同机制通过在紫外线照射部位立即形成一种免疫抑制信号来引发紫外线诱导的对接触性超敏反应的局部和全身抑制,该信号需要1至3天才能产生全身作用。