RESUMO
OBJECTIVE AND DESIGN: The present work investigates the modulation of experimental autoimmune encephalomyelitis (EAE) using genistein before the EAE induction. MATERIAL: Female C57BL/6 mice (n = 96 mice/experiment), 4-6 weeks old, were used to induce the EAE. The mice were divided into three experimental groups: non-immunized group, immunized group (EAE), and immunized and treated with genistein group (Genistein). TREATMENT: Genistein was used at a dose of 200 mg/kg s.c. and were initiated 2 days before the immunization and continued daily until day 6 postimmunization. METHODS: Animals were monitored daily for clinical signs of EAE up to day 21. Inflammatory infiltration, demyelination, Toll-like receptor (TLR) expression, cytokines and transcription factors were analyzed in spinal cords. RESULTS: The present study demonstrates, for the first time, the genistein ability to modulate the factors involved in the innate immune response in the early stages of EAE. The genistein therapy delayed the onset of the disease, with reduced inflammatory infiltration and demyelination. In addition, the expression of TLR3, TLR9 and IFN-ß were increased in genistein group, with reduction in the factors of TH1 and Th17 cells. CONCLUSION: These findings shed light on the potential of genistein as a prophylactic strategy for multiple sclerosis (MS) prevention.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Genisteína/farmacologia , Genisteína/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Receptores Toll-Like/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Esclerose Múltipla/prevenção & controle , Bainha de Mielina/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologiaRESUMO
Optical neuritis (ON) is characterized by inflammation of the optic nerve, and is one of the first clinical signs of multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is the animal model used to study MS and ON. The present study evaluated the induction, development and progression of ON using an EAE model induced by 100 µg or 300 µg of MOG35-55. An EAE model was induced in C57BL/6 mice by tail base injection of 100 µg or 300 µg of MOG35-55 in complete Freund's adjuvant, supplemented with Mycobacterium tuberculosis. On the day of injection and 48 h later, animals received intraperitoneally 300 ng of pertussis toxin. On days 7, 10, 14, 21 and 58 the optic nerve was dissected for histological analysis, production of CCL5 and immunohistochemical detection of CD4 and CD8. The histological changes observed in the optic nerves consisted of inflammatory cell infiltrates showing varying degrees of ON in the two groups. The onset of ON in the 300 µg of MOG35-55 group was coincident with higher production of CCL5, on day 10 after induction. However, the 100 µg MOG35-55 group showed more intense inflammatory infiltrate on day 14 after induction, with higher amounts of CD4 and CD8, reaching an excessive demyelination process on days 21 and 58 after induction. The results suggest that two different concentrations of MOG35-55 lead to different forms of evolution of optic neuritis.