TOLUIDINE BLUE-BASED PHOTODYNAMIC THERAPY FOR INDUCING APOPTOSIS IN ACTIVATED T-LYMPHOCYTES, AND CONSEQUENTLY FOR TREATING PSORIASIS AND FOR BONE MARROW PURGING

摘要

Photodynamic therapy is a new therapeutic modality indermatology involving the administration of a photosensitizer and itssubsequent activation with visible light to destroy or alter the function oftarget cells or tissues. Toluidine blue i(TBO) is a non-toxic cationic dye ofthe phenothiazine family. We show that toluidine blue has potentphototoxic effect against malignant human T lymphocytes in vitro.Apoptosis (DNA fragmentation and cell death) was rapidly induced byTBO in Jurkat cells. Psoriasis is an inflammatory skin disease in which therole of T lymphocytes is well established. Extensive psoriasis could be anideal indication for photodynamic therapy with whole body light exposureafter systemic photosensitizer administration. The use of human psoriaticskin-grafted SCID mice has been proven useful and reliable in the studyof novel therapeutic agents. The goal of this project is two-fold: 1) todetermine the dose-range of systemically administered toluidine blue andlight inducing a phototoxic reaction in mice 2) determine whether we caninduce clinical remission or improvement using TBO-based PDT in SCIDmice. Mice are administered TBO and irradiated with light. Psoriatic skinresponse to treatment is followed with serial clinical assessments. A dosein the µg range of TBO is to be administered systemically to psoriaticpatients. Further, the potent apoptotic effect of TBO on activatedlymphocytes T is indicative of a role of TBO for bone marrow purging. Aconcentration in the µmolar range of TBO is to be contacted with bonemarrow cells.