Phosphatidylinositol 3-OH inase (PI3K) signaling cascade plays a pivotal role in the activation of inflammatory cells. The purpose of this study was to investigate the effects of LY294002, a specific PI3K inhibitor, on airway inflammation in an in vivo mouse model of asthma.

Mice were actively sensitized by intraperitoneal injections of ovalbumin (OVA) and challenged by aerosolized OVA. Airway hyperresponsiveness was measured using a single-chamber whole-body plethysmograph, airway inflammation with influx of eosinophils was measured using differential cell counting and histological examination, and elevation in cytokine and chemokine levels in bronchoalveolar lavage (BAL) fluid was determined using ELISA.

LY294002 (1.625, 3.25 and 7.5 mg/kg) given intratracheally significantly inhibited OVA-induced airway hyperresponsiveness to inhaled methacholine in a dose-dependent manner (p<0.05). LY294002 at 7.5 mg/kg also markedly (p<0.05) attenuated OVA-induced increase in eosinophil count in BAL fluid and pulmonary eosinophilia in H&E stained lung section, and elevation of IL-13 and eotaxin levels in BAL fluid.

These results implicate that inhibition of PI3K signaling cascade may have therapeutic potential for allergic airway inflammation.