The Effect of Heparin on Antigen-Induced Mucus Hypersecretion in the Nasal Epithelium of Sensitized Rats

Abstract

Heparin is a potential anti-inflammatory drug for allergic airway inflammation. To elucidate the effects of heparin on allergic inflammation, we examined the in vivo effects of heparin on antigen-induced mucus hypersecretion and infiltration of eosinophils and neutrophils in the nasal epithelium of sensitized rats. We induced hypertrophic and metaplastic changes of goblet cells in the nasal epithelium of ovalbumin (OVA)-sensitized rats by intranasal challenge with OVA. The effects of intranasal instillation with low molecular weight heparin (LMWH; 1-1000IU/0.1ml) on mucus production and eosinophil/neutrophil infiltration were examined. Intranasal instillation with low-dose LMWH (1-10IU/0.1ml) at 30 minutes before OVA instillation stimulated OVA-induced mucus production in the nasal epithelium of sensitized rats, whereas treatment with 100IU/0.1ml LMWH showed no effect. Intranasal instillation with high-dose LMWH (1000IU/0.1ml) significantly inhibited OVA-induced mucus production. Intranasal instillation with LMWH (1-1000IU/0.1ml) dose-dependently inhibited eosinophil and neutrophil infiltration into the rat nasal mucosa. These results indicate that heparin inhibits mucus hypersecretion and infiltration of eosinophils and neutrophils in allergic inflammation, though the inhibitory effect against mucus production is obtained in high-dose heparin. Intranasal instillation with high-dose heparin may provide a new therapeutic strategy for the treatment of nasal allergic inflammation.