Ullrich S E
Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Photodermatol Photoimmunol Photomed. 1991 Jun;8(3):116-22.
Because of the undesirable side effects associated with the use of 8-methoxypsoralen and long-wave ultraviolet A (UVA) radiation in the treatment of skin disorders such as psoriasis, the use of monofunctional psoralens, which are less erythemogenic, less mutagenic, and generally non-phototoxic, has received considerable attention. Little is known, however, about the immunosuppressive properties of monofunctional psoralens. The purpose of this study was to examine the effect of parenteral administration of a monofunctional psoralen, angelicin, plus exposure to UVA radiation on the immune response. Injection of angelicin followed by exposure to UVA radiation significantly suppressed delayed-type hypersensitivity to alloantigen in a dose-dependent fashion. Similarly, the capacity of spleen cells from the angelicin and UVA-treated animals to proliferate to alloantigen was significantly suppressed. The suppression was specific for the alloantigen used to sensitize the angelicin and UVA-treated animals and was associated with the appearance of splenic antigen-specific suppressor T lymphocytes. These data demonstrate that the effect of systemic administration of a monofunctional psoralen followed by UVA exposure on the immune response is similar to that seen following the injection of bifunctional psoralens. These findings also suggest that the severe skin phototoxicity associated with the use of a bifunctional psoralen and UVA radiation is not necessary for the induction of systemic immuno-suppression. Furthermore, the induction of systemic antigen-specific immunosuppression by angelicin plus UVA, without overt skin phototoxicity, suggests the possibility of using this and related compounds to specifically inhibit unwanted immune reactions.
由于在治疗诸如牛皮癣等皮肤疾病时,使用8-甲氧基补骨脂素和长波紫外线A(UVA)辐射会产生不良副作用,因此单功能补骨脂素的使用受到了广泛关注,这类补骨脂素引起红斑的作用较小、致突变性较低且通常无光毒性。然而,关于单功能补骨脂素的免疫抑制特性却知之甚少。本研究的目的是检测肠胃外给予单功能补骨脂素当归素并暴露于UVA辐射对免疫反应的影响。注射当归素后再暴露于UVA辐射,以剂量依赖方式显著抑制了对同种异体抗原的迟发型超敏反应。同样,来自经当归素和UVA处理动物的脾细胞对同种异体抗原增殖的能力也被显著抑制。这种抑制作用对用于使经当归素和UVA处理动物致敏的同种异体抗原具有特异性,并且与脾抗原特异性抑制性T淋巴细胞的出现有关。这些数据表明,全身给予单功能补骨脂素后再暴露于UVA辐射对免疫反应的影响与注射双功能补骨脂素后所见的影响相似。这些发现还表明,使用双功能补骨脂素和UVA辐射时伴随的严重皮肤光毒性对于诱导全身免疫抑制并非必要。此外,当归素加UVA在无明显皮肤光毒性的情况下诱导全身抗原特异性免疫抑制,提示了使用这种及相关化合物特异性抑制不必要免疫反应的可能性。