Effect of benralizumab and mepolizumab on the AHR to EFS
Both benralizumab and mepolizumab inhibited the AHR mediated by the parasympathetic tone in passively sensitized bronchi.
The Emax elicited by the FRC to EFS was significantly reduced when hyperresponsive airways were incubated with benralizumab at concentrations ≥1 μg/ml (-269.36±47.21 mg/100mg bronchial tissue, P<0.001 vs. C+; Figure 4A) or mepolizumab at concentrations ≥10 μg/ml (-271.59±47.28 mg/100mg bronchial tissue, P<0.01 vs. C+; Figure 4B). Benralizumab and mepolizumab both normalized the contractile response induced by FRC to EFS in hyperresponsive ASM when these mAbs were administered at concentrations ≥10 μg/ml, leading to not significantly different FRCs compared with that inducible in C- tissue (P>0.05; Figure 4A and B). Neither benralizumab nor mepolizumab significantly modulated the potency of FRCs to EFS in passively sensitized airways (P>0.05 vs. C+). Details on the effect of different concentrations of benralizumab and mepolizumab on the contractile response to FRCs induced by EFS (Emaxand pEF50) in hyperresponsive airways are reported in e-Table 3.
The CRCs to either benralizumab or mepolizumab inhibited the contractile response to specific EFS frequencies in passively sensitized bronchi (Figure 5A-F). Specifically, both benralizumab and mepolizumab prevented the AHR in passively hyperresponsive airways stimulated by EFS delivered at EF50 (Figure 5A,D), EF70 (Figure 5B,E), and EF90 (Figure 5C,F) in a concentration-dependent manner. At EF90 benralizumab was significantly more potent (P<0.05) than mepolizumab (delta pIC50 0.45±0.16) (Table E4).