Genistein modulates the expression of Toll-like receptors in experimental autoimmune encephalomyelitis.

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.

Early IFN-γ production together with decreased expression of TLR3 and TLR9 characterizes EAE development conditional on the presence of myelin.

Experimental autoimmune encephalomyelitis (EAE) is a model for the study of multiple sclerosis, which is an inflammatory and demyelinating disease of the central nervous system (CNS). Despite increased efforts to elucidate the function of toll-like receptors (TLRs) in autoimmune diseases of the CNS, the relative contribution of other factors, including the immunomodulatory properties of TLR signaling, role of the innate response and the presence or absence of myelin peptides remain unclear. The aim was to evaluate TLR expression in the CNS during EAE development by investigating the expression of TLRs in the initial phase of EAE and establishing correlations with the modulation of inflammatory factors. Mice were subcutaneously immunized at the tail base with 100 µg of myelin oligodendrocyte glycoprotein peptide (MOG35-55), emulsified in complete Freund's adjuvant (CFA) supplemented with 400 µg of attenuated Mycobacterium tuberculosis H37RA. Pertussis toxin (300 ng per animal) was intraperitoneally injected on the day of immunization and 48 h later. Another group (MOG(-)) received an equal emulsion of CFA and M. tuberculosis, without MOG35-55, and the same protocol of Pertussis toxin. The immunized mice presented signs of disease with increased IFN-γ production and presence of NK cells on Day 2 postimmunization and reduced the expression of TLR-3 and TLR-9. In the spinal cord, CCL5 and CCL20 were higher in EAE. This study establishes a correlation between TLR-3 and TLR-9 expression with the development of EAE. In addition, evidence of a role for the myelin peptide in targeting the innate inflammatory response to the CNS is presented.

Different MOG(35-55) concentrations induce distinguishable inflammation through early regulatory response by IL-10 and TGF-ß in mice CNS despite unchanged clinical course.

Multiple sclerosis (MS) shows distinct clinical courses. Experimental autoimmune encephalomyelitis (EAE), a model to study multiple sclerosis, can be induced by different protocols, which show distinct cytokine and antibody production. The factors involved in this heterogeneity remain unclear. The relevance of MOG concentration in triggering a regulatory response in the chronic model of EAE is imprecise. The aim of this study was investigate if 100 or 300 µg of MOG(35-55) could induce different EAE profiles. Modifications in the concentration of MOG were able to change the patterns of chemokines, cytokines, percentage of cells, inflammatory infiltrate and the development of a regulatory response. However, these changes were unable to modify the intensity of response, which explains the chronic progression of the disease in both concentrations. The results presented in this study contribute to understanding the intricate mechanisms that trigger EAE and provide insights into the pathogenesis of various forms of MS.

Optical neuritis induced by different concentrations of myelin oligodendrocyte glycoprotein presents different profiles of the inflammatory process.

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.

Antimicrobianos injetáveis padronizados no HU/UFJF: utilizaçäo segura e racional (revisäo bibliográfica - 1998) / The standard use of antibiotics injected in HU/UFJF: security and rational utilization (bibliographic review - 1998)

A existência de poucas publicaçöes que permitam o rápido acesso a informaçöes sobre o uso correto e racional dos antimicrobianos injetáveis motivou o Serviço de Farmácia do HU/UFJF a elaborar uma tabela destes medicamentos à partir de uma revisäo bibliográfica, consulta à bulas de diversos fabricantes e colaboraçäo do Serviço de Doenças Infecciosas e Parasitárias do HU/UFJF. A tabela foi montada reunindo os aspectos mais questionados em nosso Serviço. Frequentemente säo solicitadas informaçöes sobre solubilidade, via de administraçäo, dose máxima, estabilidade após diluiçäo etc. Tais informaçöes objetivam assegurar o uso seguro e racional dos antimicrobianos padronizados no HU/UFJF, tendo em vista a importância de sua correta utilizaçäo e custo elevado. Este trabalho pretende apenas facilitar a obtençäo de informaçöes práticas, por isso recomendamos que algum livro texto seja consultado para informaçöes complementares.