Comparison of in vivo and in vitro inhibition of the anaphylactic mechanism by beta-adrenergic stimulants and disodium cromoglycate

Abstract

Immediate-type allergic reactions in man, rat and guinea-pig were inhibited by disodium cromoglycate (DSCG) and by β-adrenergic stimulant drugs like isoprenaline and salbutamol. Isoprenaline, like DSCG, inhibited the release of pharmacological mediators of immediate-type allergy. This anti-anaphylactic effect was shown in vivo in passive cutaneous anaphylaxis (PCA). It was also shown in the dextran-induced anaphylactoid reaction in the rat, suggesting a common pathway between this response and the true anaphylactic reaction. The dextran response in rats may perhaps be a useful screening test for potential anti-anaphylactic agents. Both DSCG and isoprenaline inhibited histamine release in a variety of in vitro test systems. In lung tissue they inhibited histamine release mediated by human reagins as well as the release of histamine mediated by γ1 antibodies in guinea-pig. The inhibition by DSCG of histamine release from guinea-pig lung contrasts with its reported lack of ability to inhibit guinea-pig PCA, and does not support the view that it specifically inhibits reactions initiated by the interaction of reaginic antibodies with antigen. Isoprenaline was at least 1000 times as potent as DSCG in all the test systems, including PCA and dextran response in rat. Thus the β-adrenergic sympathomimetics are potent protective agents against anaphylactic reactions, and should not be considered only as agents producing symptomatic relief of bronchospasm in asthma.