H2 antihistamines augment antigen-induced histamine release from human basophils in vitro.

H2 antihistamines, including cimetidine, burimamide, metiamide, and tiotidine, consistently augmented antigen-induced histamine release from human basophils in vitro when control histamine release was less than 20% of total. This effect was specific to the H2-receptor blocking activity of these drugs: equivalent degrees of receptor blockade by four different H2 antihistamines resulted in equipotent enhancement; H1-receptor antagonists did not alter histamine release; and aminoguanidine and amodiaquine, agents that inhibit histamine metabolism but do not block H2 receptors, did not enhance histamine release. Cimetidine did not enhance release when present a) when basophils were "activated" but did not release histamine ("first stage"), or b) when basophils were no longer susceptible to histamine inhibition ("second stage"). Thus, H2 antagonists enhanced histamine release by blocking the capacity of released histamine to act on H2 receptors to inhibit release. Because it is likely that only small percentages of histamine are released in vivo, it is possible that H2 antihistamines amplify the inflammatory process by blocking the inhibitory effects of the released histamine.