An α4β1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice

Inhibition of the alpha 4 subunit of both the alpha 4 beta 1 and alpha 4 beta 7 integrins has shown promise in decreasing airway inflammation and airway hyperresponsiveness in various animal models. We hypothesized that a novel, high-affinity alpha 4 beta 1 antagonist (LLP2A) would decrease the migration of eosinophils to the lung and ameliorate the airway hyperresponsiveness in a mouse model of ovalbumin-induced airway inflammation. To test this hypothesis, we administered LLP2A, or scrambled LLP2A (a negative control), prior to exposure of sensitized BALB/c mice to ovalbumin aerosol. We can partially prevent, or reverse, the airway inflammatory response, but not airways hyperresponsiveness, by treatment of mice with LLP2A, a synthetic peptidomimetic alpha 4 beta 1 antagonist. Specifically engineered, PEGylatecl (PEG) formulations of this antagonist further reduce the airway inflammatory response to ovalbumin, presumably by improving the circulating half-life of the drug. (C) 2008 Elsevier B.V. All rights reserved.