Treatment with Flt3-ligand secreting plasmid reverses allergic airway inflammation in asthma

Abstract

Rationale We have previously reported that Flt-3 Ligand (Flt3-L) prevents and reverses established allergic airway inflammation in ovalbumin (OVA) induced mouse model of asthma. In this study, we investigated the effect of pUMVC3-hFLex, a mammalian expression vector for Flt3 ligand, to examine its effect on the reversal of allergic inflammation in established asthma model in mice. Methods Allergic airway inflammation to OVA was established in Balb/c mice. OVA sensitized mice received intramuscular administration of 200μg pUMVC3-hFLex three times in ten days. Mice were then challenged with OVA and then we examined the response to pUMVC3-hFLex therapy on airway hyperresponsiveness (AHR) to methacholine and airway inflammation. Serum was collected to measure cytokines and IgE levels. Cytospin slides were prepared from bronchoalveolar lavage fluid (BALF) and total and differential cells were counted. Results pUMVC3-hFLex treatment completely reversed established AHR to methacholine (p<0.01). Plasmid administration also significantly increased serum IL-12 levels (p<0.01). Serum IL-4 and IL-5 levels were significantly reduced (P<0.05). Total number of cells in the BALF as well as BALF eosinophilia were significantly attenuated by plasmid treatment (p<0.01). Conclusions pUMVC3-hFLex treatment reverses established allergic airway inflammation in a mouse model and it might be a novel approach for treating asthma.