H2R blockade inhibits the clinical efficacy of allergen immunotherapy in a murine model of allergic asthma 3597

Abstract Description Subcutaneous immunotherapy (SCIT) is commonly used for treatment of allergic asthma. The goal of this study was to determine whether histamine signaling through H2 receptor (H2R) helps establish the clinical protection incurred by SCIT. H2R signaling can function as a negative feedback signal at multiple steps in allergy pathways, including direct suppression of mast cell activation and induction and potentiation of downregulatory cytokines. Balb/C mice were OVA-sensitized IP with OVA/Alum and then administered a 6-week course of allergen-specific SCIT in the presence or absence of H2R blockade with cimetidine, followed by intranasal challenge with OVA for 4 days. Airway hyperresponsiveness (AHR) was measured using a FlexiVent system, before and after methacholine (MCh) nebulization. At 100 mg/ml of MCh, overall resistance (Rrs) in sensitized mice increased from 2.1 after PBS challenge to 12.2 cmH2O.s/ml after OVA challenge (p = 0.01). Whereas SCIT reduced Rrs to 5.6 cmH2O.s/ml (p value vs PBS challenged mice > 0.05), mice given H2R blockade with SCIT experienced significantly increased AHR compared to PBS challenged mice (mean Rrs 14.0 cmH2O.s/ml, p < 0.01). Spectral flow cytometry demonstrated similar frequencies of inflammatory eosinophils recruited to the lungs in all OVA challenged mice. These results demonstrate that histamine signaling through H2R contributes to clinical protection induced by SCIT through a mechanism independent of effects on eosinophil recruitment. Funding Sources NHLBI/DOD Collaborative Health Initiative Research Program 1 I80 VP000002-01 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)