Gollnick S O, Liu X, Owczarczak B, Musser D A, Henderson B W
Department of Molecular Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Res. 1997 Sep 15;57(18):3904-9.
Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response that potentiates antitumor immunity but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood but are likely to involve mediation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10 but not tumor necrosis factor alpha. IL-6 mRNA and protein are strongly enhanced in the PDT-treated EMT6 tumor. PDT also increased IL-6 mRNA in exposed spleen and skin. These data suggest that the general inflammatory response to PDT may be mediated at least in part by IL-6. In addition, IL-6 may modulate the local antitumor immune response. In contrast, IL-10 mRNA in the tumor decreases following PDT. Most importantly, IL-10 is markedly induced in the skin of mice exposed to a PDT regime that strongly inhibits the CHS response, and the kinetics of IL-10 induction coincide with the known kinetics of CHS inhibition. We propose that the enhanced IL-10 expression plays a role in the observed suppression of cell-mediated responses seen following PDT.
光动力疗法(PDT)能够有效破坏恶性组织,同时还会引发复杂的免疫反应,这种反应既能增强抗肿瘤免疫力,也会抑制皮肤接触性超敏反应(CHS)并延长皮肤移植的存活时间。导致这些效应的潜在机制目前尚不清楚,但可能涉及细胞因子的介导作用。我们在BALB/c小鼠模型中证明,体内对正常组织和肿瘤组织进行光动力疗法会导致细胞因子白细胞介素(IL)-6和IL-10的表达发生显著变化,但不会影响肿瘤坏死因子α的表达。在接受光动力疗法治疗的EMT6肿瘤中,IL-6的信使核糖核酸(mRNA)和蛋白质水平显著增强。光动力疗法还会增加暴露的脾脏和皮肤中IL-6的mRNA水平。这些数据表明,对光动力疗法的一般炎症反应可能至少部分由IL-6介导。此外,IL-6可能会调节局部抗肿瘤免疫反应。相比之下,肿瘤中的IL-10 mRNA在光动力疗法后会减少。最重要的是,在接受强烈抑制CHS反应的光动力疗法方案的小鼠皮肤中,IL-10会被显著诱导,并且IL-10诱导的动力学与已知的CHS抑制动力学一致。我们认为,IL-10表达的增强在光动力疗法后观察到的细胞介导反应抑制中发挥了作用。