Modulation of the effect of histamine-releasing lymphokine on human basophils

Agents which increase or mimic intracellular cyclic 3',3'-adenosine monophosphate (cAMP) - theophylline dibutyryl cAMP (DBcAMP) and isoprenaline (in the presence of theophylline) - all produced pronounced inhibition of histamine release from human basophils, thus suggesting a regulatory role for the cAMP system. The effect of the flavonoids , quercetin and taxifolin , and the structurally-related cromone disodium cromoglycate (DSCG) was also studied. Only quercetin was effective in inhibiting histamine release. This is similar to the situation in IgE-mediated release. The microtubule stabilizer, deuterium oxide (D2O), at a concentration of 44% caused up to three-fold increase in release. This supports the belief that histamine release by this histamine-releasing factor ( HRF ) is a secretory process. Indomethacin and 5,8,11,14-eicosatetraynoic acid (ETYA), which are modulators of arachidonic acid metabolism, produced little or no inhibition of histamine release by HRF , thus suggesting that the release is largely independent of the arachidonate system, probably unlike IgE-mediated release.