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.

Serum concentration of nitric oxide in women smokers and nonsmokers with overweight / Concentración sérica de óxido nítrico en mujeres fumadoras y no fumadoras con sobrepeso

Aim: to evaluate the serum concentration of NO in overweight women, smokers (SG) and nonsmokers (NSG). Methods: blood samples from smokers (n = 20) and nonsmokers (n = 18) were collected to obtain serum, and stored at -80 ºC until analysis. NO was assessed by measuring total nitrite, determined by Greiss method. It was adopted as reference 24.4 µmol/L, mean value found in a study with healthy subjects without excess weight. We used the Student t test to compare the means of age and waist circumference, and the Mann-Whitney U test to compare the median of concentrations of nitrite, number of cigarettes/day and Body Mass Index. We adopted a significance level of p<0.05. Results: the median nitrite in SG was 16.53 (2.79 - 69.72) µmol/L, whereas in NSG was 10.85 (1.44 - 43.25) µmol/L (p = 0.028). BMI median value to SG and NSG, was respectively 29.50 (25.00 - 38.14) kg/m2 and 30.68 (25.10 - 36.98) kg/m2 (p = 0.530), being classified as overweight. The data showing that the average nitrite was below the estimated value for healthy individuals. Conclusion: the results indicate a decrease of NO metabolites in women with excess weight, independently of being smoker. Despite the significant difference found between groups, these women had values well below the reference value of NO for healthy women. Therefore, it seems that smoking does not interfere in nitrite levels in patients already compromised by obesity (AU)

Objetivo: evaluar la concentración sérica de NO en las mujeres con sobrepeso, fumadoras (SG) y no fumadoras (GSN). Método: se recogieron muestras de sangre de las fumadoras (n = 20) y no fumadoras (n = 18) para obtener el suero, y se almacenaron a -80 °C hasta su análisis. NO se evaluó mediante la medición total de nitrito, determinado por el método Greiss. Fue adoptado como referencia de 24,4 µmol/L, valor medio que se encuentra en un estudio con sujetos sanos sin exceso de peso. Se utilizó la prueba t de Student para comparar las medias de edad y la circunferencia de la cintura, así como la prueba de Mann-Whitney para comparar la mediana de las concentraciones de nitrito, número de cigarrillos/día y el Índice de Masa Corporal. Hemos adoptado un nivel de significación de p<0.05. Resultados: la mediana de SG nitrito fue 16,53 (2,79- 69,72) mol/L, mientras que en NSG fue 10,85 (1,44-43,25) µmol/L (p = 0,028). El IMC valor de la mediana de SG y NSG fue, respectivamente, 29,50 (25,00-38,14) kg/m2 y 30,68 (25,10-36,98) kg/m2 (p = 0,530), siendo clasificado como sobrepeso. Los datos muestran que el nitrito promedio estuvo por debajo del valor estimado para individuos sanos. Conclusiones: los resultados indican una disminución de los metabolitos NO en las mujeres con exceso de peso, independientemente de si son fumadoras o no. A pesar de la diferencia significativa entre los grupos, estas mujeres tenían valores muy por debajo del valor de referencia del NO para las mujeres sanas. Por lo tanto, parece que el fumar no interfiere en los niveles de nitritos en pacientes que ya están comprometidas por la obesidad (AU)