The mechanism of protection from anaphylactic shock in the guinea‐pig by pre‐treatment with anaphylatoxin

Abstract

It has been shown by Halpern & Liacopoulos (1956) that pre-treatment with repeated doses of anaphylatoxin renders the guinea-pig refractory to passive anaphylactic shock, and that this state persists for 3 weeks. It could be concluded that this effect is not due to a non-specific action of serum nor to consumption of complement. Anaphylatoxin derived from rat serum is produced by the incubation of 'Dextran' with two serum factors simultaneously, one of which is present in Cohn fraction III-0 and the other in fraction I-III-1,2,3 (Giertz, Hahn & Lange, 1956). Hahn & Oberdorf (1950) have demonstrated that antihistamine drugs inhibit shock produced by anaphylatoxin in the guinea-pig. Halpern (1956) has shown that pre-treatment with histamine liberators protects animals from passive anaphylactic shock. It has been suggested, therefore, that anaphylatoxin, acting as a histamine liberator, produces a tissue histamine depletion which interferes with the animal's reaction to anaphylactic challenge.In order to investigate this possibility, guinea-pigs have been treated, in the present experiments, with repeated intravenous injections of anaphylatoxin prepared from rat serum, and the histamine content of their tissues has been determined. Other animals were similarly treated and then subjected to passive anaphylaxis, in order to study the relationship between their histamine content and the duration and degree of protection. In addition, the lungs of several of these animals have been perfused and the histamine output after an intra-arterial injection of anaphylatoxin was compared with that produced in corresponding experiments on control untreated animals.

Factors Determining the Development of Anaphylactic Hypersensitivity in the Guinea Pig, and Their Influence on Mechanisms Involved in Desensitization

“…In animals sensitized by 500 mg of antigen, the anaphylactic hypersensitivity increased slowly throughout the period of the investigation and reached that recorded in the other two series by 16 weeks. Rates of Desensitization by Repeated Exposure to the Antigen Aerosol Investigations were performed on animals sensitized for periods of 8,28,56 or 112 days and then tested at 48-hourly intervals. Results are shown in Table II.…”

Blood and Tissue Histamine during <i>in vivo </i>Anaphylactic Shock in Susceptible and Nonsusceptible Guinea Pigs

“…Frick et al [6] have shown that anaphylatoxin will decrease lung histamine by 75 %. They concluded that 25 % of tissue histamine in the lung is 'nonliberablc'.…”