Reduction by a kallikrein inhibitor of the increased nasal airway resistance of allergic patients after antigen challenge

Abstract

Kallikrein activity in nasal lavage fluid, which was measured with a synthetic substrate, Pro-Phe-Arg-methylcoumarilamide, was increased in accordance with the severity of the symptoms of house-dust-mite allergic rhinitis. Antigen challenge was applied to patients with allergic rhinitis by placing a disk containing allergen on the nasal mucosa of the right inferior turbinate. Kallikrein activities and kinin levels in the nasal lavage fluid had increased significantly 15 min after the antigen challenge. These increases were accompanied by a marked increase in nasal airway resistance 15 min after antigen challenge. Pretreatment of the patients with camostat mesilate (60 mg/kg, p.o), a non-peptide serine proteinase inhibitor clinically used in Japan, inhibited the kallikrein activity in the nasal lavage fluid. The increase in nasal airway resistance after antigen challenge was also markedly reduced by oral administration of the inhibitor, indicating involvement of the kallikrein-kinin system in induction of the nasal symptoms.