Therapeutic effects of cisplatin on rat experimental autoimmune encephalomyelitis
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Introduction: Experimental autoimmune encephalomyelitis (EAE) is a prototypic Th1-mediated autoimmune inflammatory disease of the central nervous system (CNS), and serves as a model for the human demyelinating disease, multiple sclerosis. Cisplatin is a drug widely used in the treatment of a variety of human neoplasias, such as advanced bladder carcinoma, adrenal cortex carcinoma, breast cancer, head and neck or lung carcinoma. Cisplatin binds to DNA and interferes with cellular repair and other mechanism, which eventually result into cell death. It is known that cisplatin can induce immunosuppressive effects through inhibition of T cell activity. Therefore we analyzed the anti-inflammatory effects of cisplatin in a rat EAE model. Materials and Methods: EAE was induced in male LEW rats by immunizing with a synthetic peptide of guinea pig myelin basic protein. The development of EAE and neurological signs were evaluated by a standard protocol. Immunohistochemistry was applied to show immune cell infiltration into the CNS. Results: Early treatment of EAE rats with cisplatin effectively ameliorated the development of disease and provided a significant protective effect compared to control rats. Further, histological analysis demonstrated that the formation of the typical perivascular cuffs and brain infiltration of monocytes and lymphocytes were complete absent in cisplatin treated rats, while abundant T cell infiltration was seen in the CNS of EAE rats. Conclusions: Our data show that cisplatin has protective effects in EAE, indicating that cisplatin could be a candidate in the treatment of human CNS autoimmunity.
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Hermann J. Schluesener, Institute of Brain Research, University of Tuebingen, Calwer Str. 3, D-72076 Tuebingen, Germany