Th2 responses in OVA-sensitized BALB/c mice are down-modulated by Mycobacterium bovis BCG treatment.

OBJECTIVE: This study aimed to determine whether Mycobacterium bovis Bacillus Calmette-Guérin (BCG) treatment can reverse an established allergic airway inflammation in a BALB/c mouse model of ovalbumin (OVA)-induced airway inflammation. METHODS: OVA sensitized BALB/c mice were challenged with aerosolized OVA on days 28 to 30, 34, 41 and 63. Mice were intranasal treated with BCG on days 35 and 42. Twenty-four hours after the last challenge, blood samples were collected to detect anti-OVA immunoglobulin isotypes, and bronchoalveolar lavage (BAL) was harvested for cell count. Additionally, lungs were collected for histological analysis, detection of the eosinophil peroxidase (EPO) activity and measurement of cytokines and CCL11. The expression of CTLA-4, Foxp3 and IL-10 was also determined in lung tissue by flow cytometry. RESULTS: BCG treatment was able to inhibit an established allergic Th2-response, by decreasing the allergen-induced eosinophilic inflammation, EPO activity, levels of CCL11 and IL-4, serum levels of IgE and IgG1. Mycobacteria treatment increased lung levels of IFN-γ, IL-10 and TGF-ß, and expressions of Foxp3 and CTLA-4 in CD4(+)T cells. Additionally, an increased production of IL-10 by CD8(+) T cells was observed, even though no detectable changes in CD4(+)IL-10(+) was noticed. CONCLUSION: BCG treatment inhibits features of allergic airway inflammation and the results suggest that the mechanism underlying the down-regulatory effects of BCG on OVA-induced airway inflammation appear to be associated with the induction of both Th1 and T regulatory immune responses.

Contaminantes aéreos y sus efectos en pacientes alérgicos del Valle de Caracas / Air pollutants and their effect in allergic patients in the Valle of Caracas

La prevalencia y severidad de las enfermedades alérgicas está aumentando de manera alarmante a nivel mundial. Las principales enfermedades emergentes son las que se expresan a nivel del tracto respiratorio, por inhalación de contaminantes locales y regionales a causa de las alteraciones climáticas que se observan y registran en nuestro planeta. Numerosos artículos sobre el cambio climático y sus efectos en la reacción alérgica han aparecido en la literatura reciente, específicamente en relación con la exposición alergénica, incluyendo tipo, frecuencia, ubicación geográfica, cantidad y cualidad, en particular granos de polen debido a cambios del tiempo y duración de la estación floral de las plantas alergénicas. Las alteraciones en la vegetación son indicadores muy sensibles del cambio climático. El aumento de CO2incrementa a su vez la biomasa vegetal, la distribución de las plantas, la producción de polen y en un mayor grado, su capacidad alergénica. Otros efectos importantes se observan en la respuesta inflamatoria de la población a riesgo hacia proteínas alimentarias, alergenos de insectos y reactividad cruzada entre antígenos. Agentes como el ozono, el material particulado, el dióxido de azufre y las partículas diesel se conocen que forman especies reactivas de oxígeno, tales como el anión superóxido, el peróxido de hidrógeno y los radicales hidroxilos. Las especies reactivas de oxígeno pueden dañar proteínas, lípidos y directamente el ADN. Los contaminantes producen un efecto reversible en la función pulmonar, en el mecanismo inflamatorio de las vías aéreas, hiper-reactividad bronquial, comprometen la función inmunológica, aumentan la incidencia y exacerbación de enfermedades pulmonares como el asma y su tasa de mortalidad.

Estos agentes estimulan además, el aumento de la permeabilidad a nivel de las mucosas aéreas, lo que facilita el pase rápido de los antígenos sensibilizantes hacia capas de tejido más profundas y por consecuencia, facilitan una mayor interacción con las células del sistema inmune. Se ha propuesto un sin ergismo entre las partículas diesel y los aereo alergenos a nivel de la mucosa respiratoria alta de humanos, estimulando la producción de IgE específica por la producción de citoquinas Th2. Esto se explica por las propiedades adyuvantes de estas partículas asociadas a un aumento en la prevalencia de asma a nivel mundial, hecho relacionado al uso más frecuente de diesel en el parque automotor. Publicaciones aisladas sobre contaminantes aéreos en Venezuela, estimula la estructuración de un proyecto multidisciplinario por fases (I, II y III) de investigación, con el fin de determinar la posible influencia de los mismos, en la aparición y exacerbación de enfermedades alérgicas a nivel del tracto respiratorio, en especial los pacientes que sufren de asma en el área metropolitana de Caracas...

The prevalence and severity of allergic diseases is increasing at alarming rate worldwide. The principal emerging diseases are located in therespiratory tractdue to inhalation of localand regional pollutants as aconsequence observed and registered climate changes in our planet. Numerous articles about climate change and its effect on the allergic reaction have appeared in recent literature, specifically in relation to the allergen exposure including: type, frequency, geographical location, quantity and quality, in particular pollen grains due to changes in the weather and duration of the flowering season of allergenic plants, Changes in the vegetation are very sensitive indicators of climate change. The increase in CO2 increases the plant biomass, plant distribution, pollen production and in great degree its allergenic capacity. Other important effects are observed in the inflammatory response to proteins, insect allergens and crossed reactivity between allergens of the population at risk. Agents such as the ozone, material particles, sulphur dioxide and diesel particles are known as reactive oxygen species, such as superoxide anion, hydrogen peroxide and hydroxyl radicals. The reactive oxygen species can damage proteins, lipids an DNA directly. The pollutants produce a reversible effect on pulmonary function, the inflammatorymechanismoftheairways,producebronquial hyperreactivity, compromise the immunological function, increase the incidence and exacerbation of pulmonary diseases such as asthma and its mortality rate.

These agents also stimulate the increase in permeability of the mucosa airway, which facilitates the rapid pass and entry of antigens to the deeper layers and as a result facilitate the interaction with immune system cells. A synergism between diesel particles and air allergens in the upper human mucosa respiratory tract has been proposed and it is thought that Th2 citokines stimulate the production of specific IgE. This can be explained by the properties of these particles and their association with an increase in the asthma prevalence worldwide and the fact that there has been a more frequent use of diesel in vehicles. Publications about air pollutants in Venezuela promote that instauration of an interdisciplinary project of investigation phases (I, II, III), in order to determine their possible influence in the development and exacerbation of allergic diseases in the respiratory tract, especially in asthma patients from the metropolitan Caracas area....