Mepacrine alleviates airway hyperresponsiveness and airway inflammation in a mouse model of asthma

Asthma is a multifactorial respiratory disease. Though its incidence is increasing rapidly all over the world, the available therapeutic strategies are neither sufficient nor safe for long term use. Mepacrine, a known antimalarial drug, has been shown to possess antioxidant, anti-inflammatory, platelet anti-aggregant, and PLA(2) inhibitory activities. However, its possible use in asthma has not been studied yet. The objective of this study was to investigate the anti-asthmatic property of mepacrine using a mouse model of asthma. To accomplish this, mate BALB/c mice were sensitized and challenged with ovalbumin and treated with increasing concentrations of mepacrine. Airway hyperresponsiveness (AHR) to methacholine was assessed using unrestrained whole body plethysmography. Mepacrine (1 mg/kg) has shown marked attenuation of AHR. Cytokines such as IL-4, IL-5, IL-13 and IFN-gamma and OVA-specific IgE levels were measured in BAL (bronchoalveloar lavage) fluid and sera, respectively. Mepacrine effectively reduced the rise in IL-4, IL-5, IL-13, and OVA-specific IgE and restored IFN-gamma levels. Mepacrine also significantly prevented the increase of sPLA(2) (secretory phospholipase A(2)) activity in BAL fluid supernatant and Cys-LT (cysteinyl leukotrienes) in lung tissue homogenates of asthmatic mice. In addition, mepacrine treatment reduced BAL fluid eosinophilia and signs of allergic airway inflammation such as perivascular and peribronchial distribution of inflammatory cells. These findings indicate that mepacrine reduces the asthmatic features in ovalbumin induced asthma by acting on PLA(2)-Cys-LT axis. Thus, it could be useful for the development of better asthma therapy. (C) 2008 Published by Elsevier B.V.