RESUMEN
The prevalence of food allergy is rising in the western world. Allergen restriction is the chosen treatment in this condition, but continuous ingestion of the antigen has shown positive results in clinical trials. In a previous study, we have shown several allergic and metabolic alterations after 7 days of ovalbumin (OVA) ingestion by sensitized mice. The aim of this study was to investigate whether prolonged ingestion of antigen by sensitized mice would reverse the metabolic consequences caused by experimental food allergy. For this, allergic and metabolic parameters were analysed after prolonged ingestion of an OVA diet by OVA-sensitized mice. As shown previously, after 7 days of OVA consumption, sensitized mice showed increased serum levels of anti-OVA immunoglobulin (Ig)E and IgG1, aversion to the antigen ingestion, marked body and adipose tissue weight loss, followed by adipose tissue inflammation and decreased serum levels of adipokines, glucose and triglycerides. However, after 14 days of oral challenge, sensitized mice showed an anti-OVA IgE level similar to the mice that were only sensitized, but the specific IgG1 did not change. With this prolonged ingestion of OVA, sensitized mice were protected from OVA-induced anaphylaxis when the antigen was given systemically at a dose of 2 mg/animal. Moreover, various parameters analysed were significantly ameliorated, including adipose tissue inflammation, body and adipose tissue loss, as well as serum levels of adipokines and triglycerides. Therefore, our data suggest that prolonged ingestion of OVA by sensitized mice results in an improvement of the metabolic consequences caused by experimental food allergy.
Asunto(s)
Hipersensibilidad a los Alimentos/metabolismo , Inmunización , Ovalbúmina/inmunología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Anafilaxia/prevención & control , Alimentación Animal , Animales , Hipersensibilidad a los Alimentos/inmunología , Glucosa/metabolismo , Inmunoglobulina E/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Pérdida de PesoRESUMEN
BACKGROUND AND PURPOSE: AVE 0991 (AVE) is a non-peptide compound, mimic of the angiotensin (Ang)-(1-7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)-induced chronic allergic lung inflammation. EXPERIMENTAL APPROACH: We used BALB/c mice (6-8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 µg·mouse(-1) , i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg(-1) ·per day, s.c.) or saline (100 µL·kg(-1) ·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates. KEY RESULTS: Treatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL-5 and increased IL-10 levels in the BAL, accompanied by decreased Ang II levels in lungs. CONCLUSIONS AND IMPLICATIONS: AVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang-(1-7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma.