Study of plasmacytoid cells in multiple sclerosis: participation of indoleamine 2,3 dioxygenase in the immunological aspects of patients treated with interferon beta and Glatiramer acetate

• Grant number: 12/01155-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2012
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Leonilda Maria Barbosa dos Santos
• Grantee: Marília Domingues de Andrade
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Immunomodulators as the Type I interferons and glatiramer acetate are used as first-line drugs in the treatment of Multiple Sclerosis. Although the immunomodulator effect has been described for these two compounds, the mechanism of action is different for each product. Some observations indicate that treatment with type I IFN stimulates the synthesis of the enzyme indoleamine 2,3 dioxygenase (IDO) and the consequent activation of regulatory T cells, that diminish the inflammatory response. In addition to activating immunomodulatory mechanisms, IDO is involved in the degradation of tryptophan. The degradation of tryptophan both reduces the bioavailability of this amino acid for the synthesis of mediators such as serotonin, as can generate catabolites that are involved in mechanisms of neurodegeneration. On the other hand, some studies point to the possible neuroprotective effect of glatiramer acetate. In this proposal we aim to study two groups of patients with MS treated with IFN-² and glatiramer acetate for 12 months in order to understand the effect of these two products in the synthesis of IDO and tryptophan catabolites. We will determine the IDO produced by total leucocytes and by myeloid and plasmocytoid dedritic cells. It will be also studied the activation of regulatory T lymphocytes and the production of pro and anti-inflamatory cytokines. (AU)