Suppressive Effect of a Thioamide-Related Compound SH-2251 on a Murine Allergic Rhinitis Model

Abstract

Background: SH-2251 inhibits IL-5 production and type2 airway inflammation in a murine bronchial asthma model. However, the therapeutic effect of SH-2251 on allergic rhinitis (AR) has not been tested. We investigated whether or not SH-2251 could improve the nasal symptoms and inflammation in the nasal mucosa of a murine model of AR.Methods: AR was induced via intraperitoneal injection of ovalbumin (OVA) followed by daily intranasal challenge with OVA. SH-2251 (10 mg/kg) or vehicle (DMSO+Tween80) was administered orally once a day in the same period as the nasal challenge. Nasal symptoms were evaluated by counting the number of sneezing and nasal rubbing events on days 14, 17, 21, 28 and 35. On day 35, the levels of Il4, Il5, Il13, Ifnγ and Il1rl1 mRNA in the nasal mucosa were examined. The histological findings were examined on day 36.Results: The numbers of sneezing and nasal rubbing events were significantly decreased by the administration of SH-2251. Both eosinophil infiltration and the hickness of the nasal mucosa were improved in the SH-2251- administered mice compared that in vehicle-treated control mice. The mRNA expression of Il5, Il13 and Il1rl1 in the nasal mucosa was significantly decreased in the SH-2251-treated group compared to the vehicle group.Conclusion: These results suggest that SH-2251 may be a new therapeutic candidate for AR. In addition, SH-2251 might improve the pathogenesis of type2 chronic inflammation by targeting the IL-33 signaling via the inhibition of Il1rl1 expression.