Inhibition by Sympathomimetic Amines of Histamine Release induced by Antigen in Passively Sensitized Human Lung

Abstract

THE release of histamine after the application of antigen to a sensitized tissue provides a readily measurable index of the occurrence of a cellular anaphylactic reaction, while inhibition of the release in these conditions provides a measure of inhibition of the anaphylactic reaction. Various substances, including metabolic inhibitors, anaesthetics and antipyretics, have been found to inhibit anaphylactic histamine release¹; their 50 per cent inhibitory concentrations vary from 2 × 10⁻⁵ M to 10⁻¹ M (for example, in the actively sensitized guinea-pig lung it is 10⁻⁴ M for iodoacetate and 4 − 10⁻³ M for phenylbuta-zone). An early finding² was that adrenaline, as well as inhibiting bronchoconstriction, prevents the release of histamine during the anaphylactic reaction of isolated guinea-pig lung. Large doses of adrenaline (1 rng injected into the perfusate) were used to obtain this effect. It has also been shown³ that isoprenaline inhibits antigen-induced histamine release from actively sensitized human leucocytes, with concentrations of 2–6 × 10⁻⁴ M required for 50 per cent inhibition. We have investigated the effect of sympathomimetic amines on antigen-induced histamine release in passively sensitized human lung tissue and found that, in concentrations less than 1/1,000th of those of the most active inhibitors hitherto reported, they can prevent anaphylactic histamine release.