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

摘要

Photodynamic therapy is a new therapeutic modality in dermatology involving the administration of a photosensitizer and its subsequent activation with visible light to destroy or alter the function of target cells or tissues. Toluidine blue i(TBO) is a non-toxic cationic dye o f the phenothiazine family. We show that toluidine blue has potent phototoxic effect against malignant human T lymphocytes in vitro. Apoptosis (DNA fragmentation and cell death) was rapidly induced by TBO in Jurkat cells. Psoriasis is an inflammatory skin disease in which t he role of T lymphocytes is well established. Extensive psoriasis could be an ideal indication for photodynamic therapy with whole body light exposure after systemic photosensitizer administration. The use of human psoriatic skin-grafted SCID mice has been proven useful and reliable in the study of novel therapeutic agents. The goal of this project is two-fold: 1) to determine the dose-range of systemically administered toluidine blue and light inducing a phototoxic reaction in mice 2) determine whether we can induce clinical remission or improvement using TBO-based PDT in SCID mice. Mice are administered TBO and irradiated with light. Psoriatic skin response to treatment is followed with serial clinical assessments. A dose in the .mu.g range of TBO isto be administered systemically to psoriatic patients. Further, the potent apoptotic effect of TBO on activated lymphocytes T is indicative of a role of TBO for bone marrow purging. A concentration in the .mu.molar range of TBO is to be contacted with bone marrow cells.