Hayami Junji, Okamoto Hiroyuki, Sugihara Akira, Horio Takeshi
Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, Japan.
J Dermatol. 2007 May;34(5):320-7. doi: 10.1111/j.1346-8138.2007.00280.x.
Photodynamic therapy (PDT) has been used for inflammatory skin disorders as well as superficial skin cancers such as solar keratosis and Bowen's disease. Whether PDT with topical application of aminolevulinic acid (ALA) and exposure to visible light has a similar immunosuppressive action to ultraviolet phototherapy was investigated using a murine contact hypersensitivity (CHS) model. The number of epidermal Langerhans cells (LC) was decreased with their morphological changes 1 day after PDT with the minimal level at 5 days and gradual recovery thereafter. Conversely, the number of CD11c(+) I-A(+) cells was significantly increased in the draining lymph nodes after PDT. This suggests that LC moved from PDT-treated skin, resulting in the decrement of epidermal LC and migration to lymph nodes. CHS response to DNFB applied on the PDT-treated skin with 20% ALA and 40 J/cm(2) visible light was significantly suppressed (local immunosuppression). When mice were treated with 80 J/cm(2) of PDT, CHS response to the antigen applied on untreated distant skin was also significantly suppressed (systemic immunosuppression). The locally or systemically immunosuppressed mice by PDT were attempted to sensitize again with DNFB on non-treated skin, but elicitation responses were significantly suppressed. However, these mice were able to be sensitized with another hapten, oxasolone. Thus, a hapten-specific immunological unresponsiveness (tolerance) was induced in mice by topical ALA-PDT. These findings suggest that PDT has a potential immunological contribution to clinical efficacy for inflammatory diseases identical to ultraviolet phototherapies.
光动力疗法（PDT）已被用于治疗炎症性皮肤病以及浅表皮肤癌，如日光性角化病和鲍恩病。我们使用小鼠接触性超敏反应（CHS）模型研究了局部应用氨基乙酰丙酸（ALA）并暴露于可见光下的PDT是否具有与紫外线光疗相似的免疫抑制作用。PDT治疗1天后，表皮朗格汉斯细胞（LC）数量减少，形态发生改变，5天时降至最低水平，此后逐渐恢复。相反，PDT治疗后引流淋巴结中CD11c(+) I-A(+)细胞数量显著增加。这表明LC从PDT治疗的皮肤迁移，导致表皮LC数量减少并迁移至淋巴结。用20% ALA和40 J/cm(2)可见光对PDT治疗的皮肤进行二硝基氟苯（DNFB）处理后，CHS反应受到显著抑制（局部免疫抑制）。当用80 J/cm(2)的PDT处理小鼠时，对未处理的远处皮肤施加抗原后的CHS反应也受到显著抑制（全身免疫抑制）。通过PDT局部或全身免疫抑制的小鼠试图在未处理的皮肤上再次用DNFB致敏，但激发反应受到显著抑制。然而，这些小鼠能够用另一种半抗原恶唑酮致敏。因此，局部应用ALA-PDT可在小鼠中诱导半抗原特异性免疫无反应性（耐受性）。这些发现表明，PDT对炎症性疾病的临床疗效具有潜在的免疫学贡献，与紫外线光疗相同。
