Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H 1-antihistamines

Abstract

Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H 1-antihistamine. Intradermal injection of 100μl of 100μg/ml histamine and 10mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1×10 -4 and 1×10 -5m caused significant (P<0.05) histamine release from isolated human cutaneous mast cells. In conclusion, icatibant induces histamine-mediated wheal and flare responses that may be reduced in severity by prophylactic administration of an H 1-antihistamine. © 2011 John Wiley & Sons A/S.