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).