For the evaluation of anti-allergic effect of drugs, it is necessary to work out quantitatively in some allergic reaction system in vivo. For this purpose, passive cutaneous anaphylaxis (PCA) is considered preferable. This is because it would be possible to determine the degree of reaction exactly in terms of the amount of dye infiltrated in the skin; although the extraction of the dye has been a very difficult problem. At the beginning of this investigation, therefore, we searched for a good method to extract the dye and obtained an easy and satisfactory one. Based on the establishment of this method, which is described below, the authors set out a series of experiments to evaluate the drug action against PCA. It is desirable to see whether cutaneous anaphylaxis corresponds in every respect to systemic anaphylaxis. Therefore, the action of drugs was also examined against passive systemic anaphylaxis (PSA). In this paper, as the first attempt, the effect of anti-histaminics was tested in guinea-pigs, as histamine is assumed to be the chief mediator in the anaphylactic reaction in guinea-pigs. Throughout the experiments in this report, bovine γ-globulin (BGG) and rabbit anti-BGG serum were used as antigen and antibody respectively. The results are summarized as follows: 1) The following precedure was proved to be satisfactory to extract the infiltrated dye. That is, the infiltrated dye, Evans blue, was easily and quantitatively extracted from the skin by stirring the chopped tissue in a homoblender with the mixture of acetone and aqueous solution of the detergent "Emal S" (Kao Soap Co.). After centrifugation, the dye was determined by measuring the optical density at 620mμ of the supernatant. 2) When administered intraperitoenally, all the three anti-histaminics (promethazin, triploridine and diphenhydramine) inhibited histamine injected intradermally very strongly. On the other hand, PCA was considerably inhibited by higher doses of promethazine (>5mg/kg) but was affected only a little by triploridine and diphenhydramine, when administeread 1 hour before the injection of antige. 3) Contrary to the intraperitoneal injection, intradermal administration of a very small amount of these drugs together with antiserum caused a conspicuous inhibition of PCA. This inhibition was obvious when antigen and the dye were given immediately after the intradermal injection of a drug mixed with antiserum. Accordingly, it may be considered that the liberation of histamine contributes something to the manifestation of PCA in guinea-pigs. 4) PSA were clearly inhibited by the intraperitoneal injection of promethazine or triploridine, though only slightly by diphenhydramine. Therefore, it may be assumed that histamine is the main mediator in PSA.
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