Influence of Histamine H1 Receptor Antagonists on Thioredoxin Production In vitro and In vivo

Background: Thioredoxin (TRX), a 12-kDa oxidoreductase enzyme, is well known to be a redox-active protein that regulates reactive oxidative metabolism. TRX is also accepted to be a protein with anti-inflammatory effects and reported to attenuate the development of allergic airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although histamine H1 receptor antagonists are frequently used for the treatment of AR, the influence of the agents on TRX production is not well understood. In the present study, we examined the influence of fexofenadine (FEX), cetirizine (CT), and levocetirizine (LCT), which are classified into histamine H1 receptor antagonists, on TRX production in vitro and in vivo. Methods: Macrophages derived from THP-1 cells (1 × 105 cells/ml) were cultured with 50 μM H2O2 in combination with/without the agents for 24 h. Nasal secretions were obtained from patients with Japanese cedar pollen-sensitized rhinitis, who were treated with FEX or LCT for four weeks during pollen season. TRX contents in both culture supernatants and nasal secretions were examined by ELISA. Results: Addition of FEX, CT and LCT into macrophage cultures increased TRX levels in supernatants. The minimum concentration of the agents that caused significant increase was 0.3 μM for FEX, 0.4 μM for CT and LCT. Treatment of patients with FEX and LCT also caused increase in TRX levels in nasal secretions along with attenuation of clinical symptoms. Conclusion: Histamine H1 receptor antagonists may increase the ability of macrophages to produce TRX, and results in favorable modification of clinical conditions of AR.