Estratégias tolerogênicas antígeno-específicas visando profilaxia e terapia na artrite autoimune experimental

• Ano de defesa: 2014
• Autor(a) principal: Ishikawa, Larissa Lumi Watanabe [UNESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Artrite reumatóide; Doenças auto-imunes; Proteoglicanos; Tolerancia imunologica; Vitamina D; Rheumatoid arthritis
• Link de acesso: http://hdl.handle.net/11449/124050

Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints. Most of the therapies used for RA treatment are based on general suppression of immune response, which may increase the susceptibility to infectious agents. The main objective of this work was to establish specific tolerogenic strategies for prophylaxis or therapy of RA. For this purpose, we first established a model of arthritis induced by bovine proteoglycan (PG). Female BALB/c retired breeder mice immunized with bovine PG associated with dimethyl-dioctadecyl ammonium bromide adjuvant developed a typical arthritis characterized by erythema and edema resulting from joint inflammation of one or more paws. Histopathological analysis showed the presence of synovial membrane hyperplasia, inflammatory infiltrates (pannus formation), cartilage destruction and bone erosion. Disease incidence was 100% and the arthritic mice produced significant levels of pro and anti-inflammatory cytokines and IgG1 and IgG2a anti-PG antibodies. Further, we tested the prophylactic potential of PG. Three doses of 50 μg of PG determined a prophylactic effect characterized by a significant decrease in both, arthritis incidence and clinical scores. The decrease in IFN-g and IL-17, as well as the increase in IL-5 and IL-10 production by spleen cells stimulated with PG may be contributing to the prophylactic effect observed in this group. Lastly, we evaluated the therapeutic potential of the combination of active vitamin D (VitD3) with PG. The VitD3+PG association determined a therapeutic effect in experimental arthritis. There was a significant decrease in the clinical scores after VitD3+PG treatment that was confirmed by the histopathological analysis. Most mice paws from the treated group presented well preserved joint structures that were similar to the ones present in healthy animals. Both pro and anti-inflammatory cytokines were decreased after this treatment. No differences were ...