Effect of benralizumab and mepolizumab on the AHR to
histamine
Both benralizumab and mepolizumab inhibited the AHR mediated by the
histaminergic tone in passively sensitized bronchi.
The Emax elicited by the CRC to histamine was
significantly reduced when passively sensitized airways were incubated
with benralizumab at concentrations ≥1 μg/ml (-1348.33±126.51 mg/100mg
bronchial tissue, P<0.001 vs. C+; Figure 2A), whereas at least
3 μg/ml of mepolizumab were necessary to significantly inhibit the
histamine mediated AHR (-954.59±333.13 mg/100mg bronchial tissue,
P<0.001 vs. C+; Figure 2B). When either benralizumab or
mepolizumab were administered at concentrations ≥10 μg/ml, the AHR
induced by CRC to histamine in passively sensitized bronchi was
completely prevented, with the contractile response of hyperresponsive
ASM reduced at the same level of that detectable in C- airways
(P>0.05 vs. C-), or even significantly lower for
benralizumab administered at 100 μg/ml (P<0.05 vs. C-) (Figure
2A and B). Benralizumab administered at concentrations ≥10 μg/ml
significantly (delta pEC50 0.65±0.20, P<0.05
vs. C+) reduced the potency of histamine in passively sensitized
airways, whereas 100 μg/ml of mepolizumab were necessary to elicit the
same significant impact (delta pEC50 0.65±0.22,
P<0.05 vs. C+) on the pEC50 of histamine.
Details on the effect of different concentrations of benralizumab and
mepolizumab on the pharmacological characteristics of CRC to histamine
(Emax and pEC50) in passively sensitized
bronchi are reported in Table 1.
The CRCs to either benralizumab or mepolizumab modulated the contractile
plateau to specific concentrations of histamine in hyperresponsive
airways (Figure 3A-F). Specifically, both benralizumab and mepolizumab
prevented the AHR in passively sensitized airways contracted by
histamine administered at EC50 (Figure 3A,D),
EC70 (Figure 3B,E), and EC90 (Figure
3C,F) in a potent concentration-dependent manner. Benralizumab resulted
0.73±0.10 logarithm significantly (P<0.05) more potent than
mepolizumab (Table 2).