Inhibition of hematopoietic prostaglandin D synthase improves allergic nasal blockage in guinea pigs

► TFC-007 was a selective inhibitor for H-PGDS. ► TFC-007 suppressed allergic PGD 2 production in the nasal tissue in guinea pigs. ► Allergic late phase nasal blockage was inhibited by a pre-treatment with TFC-007. ► A treatment with TFC-007 after an antigen challenge did not affect the nasal sign. ► Allergic nasal eosinophilia was not affected by TFC-007. Although it has been suggested that prostaglandin (PG) D 2 is involved in the pathogenesis of allergic rhinitis, whether the inhibition of hematopoietic PGD 2 synthase (H-PGDS) shows beneficial effects on allergic rhinitis has been unclear. We evaluated the effects of a selective H-PGDS inhibitor, TFC-007, on nasal symptoms on Japanese cedar pollen-induced allergic rhinitis of guinea pigs. Sensitized animals were challenged with the pollen once a week. TFC-007 (30 mg/kg, p.o.) given once before a challenge almost completely suppressed PGD 2 production in the nasal tissue early and late after the challenge. Although pre-treatment did not affect the incidences of sneezing and early phase nasal blockage, late phase nasal blockage was partially but significantly attenuated; however, nasal eosinophilia was not suppressed. In contrast, when TFC-007 was given once 1.5 h after the challenge, the late phase response was not affected. Collectively, PGD 2 produced by H-PGDS early after an antigen challenge can participate in the induction of late phase nasal blockage, although the mechanism may be independent of eosinophil infilatration. The strategy for H-PGDS inhibition may be beneficial for allergic rhinitis therapy.