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

Although it has been suggested that prostaglandin (PG) D2 is involved in the pathogenesis of allergic rhinitis, whether the inhibition of hematopoietic PGD2 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 PGD2 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, PGD2 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.

► TFC-007 was a selective inhibitor for H-PGDS. ► TFC-007 suppressed allergic PGD2 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.