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Studies in Anaphylaxis

The Relation of Certain Drugs to the Anaphylactic Reaction, and the Bearing Thereof on the Mechanism of Anaphylactic Shock

From the Pharmacological Laboratory of the University of Nebraska, Medical College, Omaha

Abstract

Guinea-pigs and rabbits sensitized to ox serum or horse serum, and treated subcutaneously with moderate doses of quinine preceding the reinjection of the specific antigen, have their susceptibility increased from 3 to 10 times to the specific protein, as compared with control sensitized animals.

No appreciable degree of proteolysis could be demonstrated to occur in vitro by treating sensitized serum with the specific antigen, whether incubated alone or with quinine. The augmented susceptibility of sensitized animals to the specific protein when under the influence of quinine cannot, therefore, be referred to the well known action of this drug on ferments.

Quinine added to Ringer-Locke solution perfused through the pulmonary vessels of sensitized or normal rabbits does not cause any noticeable constriction of these vessels. Specific foreign protein added to Ringer-Locke solution perfused through the pulmonary vessels of sensitized rabbits produces pulmonary obstruction to a marked degree. The altered susceptibility of sensitized animals to the foreign protein produced by quinine cannot be referred to any synnergy between quinine and the anaphylactic process on the pulmonary circulation.

It has been suggested that histamine might be the causative factor of anaphylactic shock. On closer investigation it does not appear that histamine is identical with the anaphylactic process, for the following reasons:

a. Histamine does not produce in animals the temperature reactions observed in anaphylaxis.

b. Histamine does not alter the coagulability of the blood, as is noted in anaphylactic shock.

c. Quinine alters markedly the course of the anaphylactic reaction, by augmenting the susceptibility of sensitized animals to the foreign protein; it has no harmful effect on the course of intoxication with histamine.

d. There is no relation between histamine and antianaphylaxis. Neither does desensitization influence the toxicity of histamine, nor does the preliminary treatment with histamine alter the lethal dose of the specific foreign protein in sensitized animals.

A synnergetic relation is shown to exist between histamine and the specific foreign protein in sensitized guinea-pigs. This is probably best explained on the assumption that some points of attack of histamine and of the anaphylactic process are identical.