PT - JOURNAL ARTICLE AU - Edward Barrett AU - Karin Rudolph AU - Chris Royer AU - T. Ly AU - S. Boehme AU - Kevin Bacon TI - Effect of CCR3 inhibitors on allergic airway responses in ascaris-sensitized cynomolgus monkeys DP - 2012 Sep 01 TA - European Respiratory Journal PG - P2138 VI - 40 IP - Suppl 56 4099 - http://erj.ersjournals.com/content/40/Suppl_56/P2138.short 4100 - http://erj.ersjournals.com/content/40/Suppl_56/P2138.full SO - Eur Respir J2012 Sep 01; 40 AB - Aim: CCR3 has historically been associated with the functional responses of eosinophils in various models of allergic disease. The goal of this study was to determine whether pre-treatment with CCR3 inhibitors via oral and inhaled routes attenuates asthma responses in ascaris sensitized Cynomolgus monkeys.Methods: Animals received a CCR3 antagonist given orally (AP0), or by inhalation (AR1) once or twice a day for 10 or up to 21 days prior to inhaled ascaris challenge. Changes in airway function (immediate and methacholine [MCh]) and inflammation (BAL & blood cells) were evaluated.Results: Oral (AP0 5 mg/kg; BID 10 days) or inhaled (AR1 860 μg; BID 7 days) treatment showed a trend towards a reduced immediate ascaris and MCh response but did not reach statistical significance. A longer oral treatment (AP0 3 mg/kg; QD 20 days) resulted in a significant reduction in both immediate bronchoconstriction and AHR. This was not associated with a consistent effect on BAL or blood eosinophils, but reduced the lymphocyte, macrophage and mast cell numbers. AP0 given in combination with inhaled fluticasone (79 μg BID) did not yield in a significant additive or synergistic effect on airway function but did lead to a greater reduction in BAL and blood eosinophils than AP0 or fluticasone alone.Conclusion: Treatment with a CCR3 inhibitor in the non-human primates, Ascaris model of asthma, shows that a number of critical parameters can be affected which are significantly different to alterations in the recruitment of eosinophils. Overall, these observations suggest that CCR3 inhibition may have more globally-beneficial responses in an asthmatic setting than previously appreciated.