Asthma is a disease of airway inflammation that in most cases fails to resolve. The resolution of inflammation is an active process governed by specific chemical mediators, including D-series resolvins. In this study, we determined the impact of resolvin D1 (RvD1) and aspirin-triggered RvD1 (AT-RvD1) on the development of allergic airway responses and their resolution. Mice were allergen sensitized, and RvD1, AT-RvD1 (1, 10, or 100 ng), or vehicle was administered at select intervals before or after aerosol allergen challenge. RvD1 markedly decreased airway eosinophilia and mucus metaplasia, in part by decreasing IL-5 and IκBα degradation. For the resolution of established allergic airway responses, AT-RvD1 was even more efficacious than RvD1, leading to a marked decrease in the resolution interval for lung eosinophilia, decrements in select inflammatory peptide and lipid mediators, and more rapid resolution of airway hyperreactivity to methacholine. Relative to RvD1, AT-RvD1 resisted metabolic inactivation by macrophages, and AT-RvD1 significantly enhanced macrophage phagocytosis of IgG-OVA–coated beads in vitro and in vivo, a new proresolving mechanism for the clearance of allergen from the airways. In conclusion, RvD1 and AT-RvD1 can serve as important modulators of allergic airway responses by decreasing eosinophils and proinflammatory mediators and promoting macrophage clearance of allergen. Together, these findings identify D-series resolvins as potential proresolving therapeutic agents for allergic responses.

Quercetin and isoquercitrin are effective eosinophilic inflammation suppressors, suggesting a potential for treating allergies.

No abstract

Quercetin is a plant-derived flavonoid widely known by its anti-oxidant and anti-inflammatory properties, but its oral bioavailability is very poor and this becomes difficult to assess its therapeutic potential. Here we have compared the anti-inflammatory effect of quercetin-loaded microemulsion (QU-ME) and quercetin suspension (QU-SP) in an experimental model of airways allergic inflammation. Mice received daily oral doses of QU-ME (3 or 10mg/kg; in an oil-in-water microemulsion content 0.02:0.2:1 of lecithin:castor oil:Solutol HS15((R))), QU-SP [10mg/kg, in carboxymethylcellulose (CMC) 0.5% in water] or vehicle from the 18th to the 22nd day after the first immunization with ovalbumin (OVA). Dexamethasone was used as positive control drug. Every parameter was evaluated in the 22nd day (24h after the second OVA-challenge). We have also tried to assess by HPLC-MS a quercetin metabolite in the blood of rats treated with QU-SP or QU-ME. QU-ME was better orally absorbed when compared with QU-SP. Furthermore, oral administration of QU-SP failed to interfere with leukocyte recruitment, while QU-ME inhibited in a dose-dependent way, the eosinophil recruitment to the bronchoalveolar lavage fluid (BALF). QU-ME also significantly reduced both IL-5 and IL-4 levels, but failed to interfere with CCL11, IFN-gamma and LTB(4) levels. In addition, QU-ME oral treatment inhibited the nuclear transcription factor kappa B (NF-kappaB) activation, P-selectin expression and the mucus production in the lung. The present results show that QU-ME exhibits pronounced anti-inflammatory properties in a murine model of airways allergic inflammation and suggest that it might present therapeutic potential for the airways inflammatory diseases management.