Estudo comparativo de parâmetros inflamatórios nos modelos experimentais de inflamação pulmonar alérgica aguda e crônica.

Abstract

Eosinophilic lung inflammation of the lower airways, is the central feature in the pathophysiological mechanisms of allergic asthma. Asthma affects about 300 million people worldwide, and approximately 250,000 deaths are attributed to the disease annually. In vivo experimental models of acute and chronic lower airway allergic inflammation present similarities in clinical and pathophysiological signs of disease in humans, which makes it possible to understand the mechanisms of the disease, in addition to making preclinical tests more effective. The goal of the present study was to evaluate and to compare the inflammatory and allergic parameters of different experimental models of acute allergic pulmonary inflammation (23 days of sensitization and challenge with the allergen) and chronic (35 days of sensitization and challenge with the allergen). Female BALB / c mice were sensitized and challenged with ovalbumin (OVA) and the inflammatory parameters observed were leukocyte migration in the bronchoalveolar lavage fluid (BALF), histopathological events as inflammation, mucus and tissue remodeling and the allergic parameters evaluated were specific IgE-OVA production and Th2 cytokine profile (IL-4 and IL-13). The prolonged OVA challenged, in the chronic allergic asthma protocol (35 days), induced a significant leukocyte recruitment into the BALF (8.63x105 ± 0.81 vs 5.63x105 ± 0.457), histological alterations (score = 6.75 ± 0.25 vs 4.5 ± 0.299) and mucus hyperproduction (3.25 ± 0.25 vs 0.5 ± 0.289) as compared to the OVA group of the acute allergic asthma protocol (23 days). In addition, it was verified that in OVA group of the chronic presented a marked tissue remodeling, which was not observed in the OVA group of the acute protocol (score = 2.75 ± 0.25 vs 0.25 ± 0.25). Additionally, it was observed that on both protocols (23- and 35-days) production of IgE-OVA specific (3822 ± 274 and 3947 ± 149, respectively), IL-4 cytokines (51.7 ± 2.63 and 52.7 ± 4.15, respectively) and IL-13 (66.4 ± 1.84 and 78.2 ± 1.75, respectively) comparing with the basal groups. By demonstrating, with these results, that the increase in IL-13 was more pronounced (p<0,01) in intense allergic exposed animals (23 days compared to 35 days). The results obtained in this study demonstrate that the prolonged allergen challenge promotes the exacerbation of the chronic inflammatory parameters of the lower airways, characteristic of allergic asthma.