Immunomodulatory effect of hydroxychloroquine in experimental autoimmune arthritis

• Grant number: 14/15775-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2014
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexandrina Sartori
• Grantee: Larissa Lumi Watanabe Ishikawa
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mainly affects the small joints. If not properly treated, the persistent inflammatory process may progress to joint destruction and subsequent disability. RA treatment is complex and remains a major scientific challenge. In this context, the main objective of this project is to investigate the therapeutic and the immunomodulatory effect of the antimalarial drug, hydroxychloroquine (HCQ), in an experimental model of RA. For arthritis induction, DBA/1 mice will be immunized with type II collagen associated with Complete Freund's Adjuvant. HCQ treatment will be performed after the onset of the disease. The therapeutic effect will be evaluated by clinical score and histopathological analysis, while the imunommodulatory effect will be investigated by cytokine production and characterization of dendritic cells (DCs) and T cell subsets in the spleen and joints. Our expectation is to understand, at least partially, the mechanisms involved in the immunomodulatory effect of HCQ on RA, which is still not fully elucidated. Thus, the effect of HCQ on DCs and regulatory T cells will be also evaluated in vitro. (AU)