Pharmacological analysis
The ASM contractile force in response to histamine, EFS, and QS was
reported as mg normalized for 100 mg of bronchial tissue (mg/100mg). The
protective effect of benralizumab and mepolizumab against AHR induced by
contractile stimuli in passively sensitized airways was expressed as the
percentage of the maximal AHR inhibition, that in turn was identified as
the delta between the AHR induced in C+ airways and the normal
contractile response elicited in C- airways. Since the effect of each
single concentration of the mAbs investigated in this research was
tested after overnight incubation during the sensitizing procedure, the
CRCs to benralizumab and mepolizumab on the contractile plateau to
specific histamine concentrations and EFS frequencies were generated by
plotting in the same graph the data originated from different bronchial
rings treated with different concentrations of the mAbs. Appropriate
curve-fitting to sigmoidal models were used to calculate the effect (E),
Emax, EC50, EC70,
EC90, EF50, EF70,
EF90, and the half maximal inhibitory concentration
(IC50). The equations used to describe the models used
in this study were:
Y=Bottom + (Top-Bottom)/(1+10^((LogEC50_or_EF50-X)))
and Y=Bottom + (Top-Bottom)/(1+10^((X-LogIC50))).
EC50, EF50, and IC50were transformed in pEC50 (-LogEC50),
pEF50 (-LogEF50), and
pIC50 (-LogIC50) to perform the
statistical analysis of the potency .
Data originated from ELISA kits were elaborated after normalization for
the wet weight (100 mg) of isolated airways.