Effect of benralizumab and mepolizumab on the levels of cAMP in hyperresponsive airways
Both benralizumab and mepolizumab prevented the cAMP depletion elicited by passive sensitization in hyperresponsive bronchi, by normalizing the concentrations of cAMP when administered at 10 μg/ml (P>0.05 vs. C-). At concentrations ≥30 μg/ml both the mAbs restored the cAMP concentrations at levels significantly higher than those detected in C+ tissue (benralizumab +63.00±4.96 %, P<0.01 vs. C+; mepolizumab +47.05±4.66 %, P<0.05 vs. C+) (Figure 7A). Benralizumab at 100 μg/ml, but not mepolizumab, increased the cAMP concentrations at a level significantly (P<0.05) greater than that found in C- tissue.
The levels of cAMP were significantly correlated with the inhibition of AHR to QS induced by benralizumab and mepolizumab (y=1.52±0.12x+1.65; R2 0.94; P<0.001) (Figure 7B).