Characterization of augmentation of allergic and non-allergic histamine release by non-steroidal anti-inflammatory/analgesic agents.

Augmentation of allergic histamine release from human leukocytes previously was shown to be produced by numerous acidic anti-inflammatory/analgesic agents. In the present study, cicloprofen or diclofenac, representative of the arylalkanoic and anthranilic acids, respectively, augmented the antigen-dependent first stage and the calcium-dependent second stage of allergic histamine release. Both agents enhanced the rate and total amount of histamine release in the whole reaction. Further, it was demonstrated that augmentation could occur in a specific, non-cytolytic manner. In extended studies, cicloprofen and diclofenac augmented ionophore (A23187)- and concanavalin A-induced histamine release from human leukocytes and ionophore-induced release from rat mast cells. Concanavalin A- and ovalbumin-induced release from rat mast cells were inhibited by cicloprofen and diclofenac. These findings define systems useful for the study of the mechanisms of action of the acidic anti-inflammatory agents.