ABSTRACT
Ketotifen is an antiallergic drug and may have direct inhibitory effects on eosinophils. To investigate the anti-eosinophilic effect of ketotifen, we examined the effect of ketotifen on the production of reactive oxygen species (ROS) from eotaxin-primed human eosinophils. Ketotifen at 10(-10)-10(-6) mol/l significantly reduced the production of ROS evoked by A23187 from eosinophils primed by eotaxin. In contrast, ketotifen at 10(-5) mol/l significantly augmented the production in the absence of eotaxin. We demonstrated that appropriate concentrations of ketotifen may have direct inhibitory effects on eosinophil oxidative metabolism primed by eotaxin. Ketotifen may contribute to the treatment of allergic disease through its anti-eosinophilic effects.
Subject(s)
Anti-Allergic Agents/pharmacology , Chemokines, CC/pharmacology , Eosinophils/drug effects , Ketotifen/pharmacology , Reactive Oxygen Species/metabolism , Anti-Allergic Agents/administration & dosage , Calcimycin/pharmacology , Chemokine CCL11 , Chemokines, CC/physiology , Dose-Response Relationship, Drug , Eosinophils/metabolism , Humans , In Vitro Techniques , Ionophores/pharmacology , Ketotifen/administration & dosageABSTRACT
The pathogenesis of bronchial asthma is chronic airway inflammation caused by immune cells such as T lymphocytes and eosinophils. Eosinophils release cytotoxic products including reactive oxygen species at the site of inflammation, leading to epithelial damage. Human thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced and secreted from cells by oxidative stress. This study was undertaken to investigate the clinical significance of TRX in the pathogenesis of asthma. We collected blood samples from 48 patients with bronchial asthma with or without attack, and measured serum ECP and pulmonary function as well as serum TRX. The serum TRX levels in patients with asthma were significantly increased in patients with mild (34.63 [28.40-42.73] ng/ml, medians with 25 and 75% interquartiles, P=0.0064) and moderate (38.83 [35.14-50.80] ng/ml, P=0.0017) asthma attacks compared with those during the asymptomatic period. The serum TRX levels were inversely correlated with FEV(1.0)% (r=-0.44, P=0.039) and %PEF (r=-0.49, P=0.020) during attack. There was a significant correlation between the serum TRX and the serum eosinophil cationic protein (rs=0.32, P=0.016). These findings suggest that serum TRX is related to the state of asthma exacerbation and allergic inflammation.
