Summary and Discussion
In 18 dogs sensitized to horse-serum two different blockading agents (Indian ink and saccharated iron oxide) were administered by various methods. Moderately severe to fatal reactions were produced in 15, a questionable reaction in one, and no evidence of shock in 2. Of these latter the incubationary period of 102 days in experiment 190 is so long as to raise doubt concerning the validity of the experiment. The percentile distribution of the varying degrees of shock in 59 control animals was as follows: ++++ = 28, +++ = 13, ++ = 48, + = 8, 0 = 3. The corresponding percentages in the experimental series are respectively 38, 22, 22, 5 and 11. There is a slight shift in the direction of increased severity of reaction, but we do not believe the difference is great enough to be significant. There is thus no indication from these experiments as a whole that reticulo-endothelial blockade in any way modifies the reaction resulting in anaphylactic shock. Use of the bromsulphalein dye-retention test as a measure of the degree of blockade produced by the various agents and methods of administration gave no indication of any relationship between the degree of blockade and the severity of the shock. Fatal reactions occurred as frequently in the animals with marked retention of dye as in those with comparatively little retention. In 2 experiments the animals were blockaded prior to the administration of the sensitizing injections with no apparent effect upon the sensitization as judged by the subsequent shocks. We are thus unable to confirm the report of Petersen, Jaffe, Levinson and Hughes that reticulo-endothelial blockade diminishes the anaphylactic reaction in dogs. These workers used only 5 animals, the antigen used was egg-white which has been reported to be anaphylactogenically inferior to horse-serum for the dog (6), and the criterion used for measuring shock was a chemical study of lymph from the thoracic duct. No direct comparison of results is therefore possible. With regard to the relatively extensive literature on anaphylaxis and reticulo-endothelial blockade in other laboratory animals there are contradictory reports (1). The methods of blockade have varied with respect to the routes of administration (e.g., subcutaneous, intraabdominal, and intravenous), different blockading agents have been used, and the shocking dose of antigen has been administered subcutaneously, intraabdominally or intravenously. It is therefore difficult to compare most of these reports. It has, however, occurred to us that in many experiments in which the shocking dose of antigen has been given other than intravenously, that the reported protection against anaphylactic shock has been possibly due to a reduced or delayed absorption of the antigen rather than to a specific effect upon the anaphylactic reaction. In some of our experiments on rabbits and guinea pigs this has seemed to be the case. In 7 horse-serum sensitized guinea pigs in which Indian ink was injected intraabdominally on the last 2 days of the incubationary period, the intraabdominal injection of horse-serum provoked no anaphylactic symptoms, while all of the 7 controls showed definite symptoms and 2 had fatal reactions. In 8 horse-serum sensitized rabbits that had received intraabdominal injections of Indian ink, the intraabdominal test injection of horse-serum was followed by shock in 2. Of the remaining six, 4 showed definite symptoms when subsequently injected intravenously. In 7 control horse-serum sensitized rabbits, the intraabdominal injection was followed by symptoms of shock in 5. Of the remaining 2, one showed symptoms following intravenous injection. These experiments are not sufficiently numerous to warrant final conclusions but we believe that the simplest explanation of these results is that the ink in these experiments in some way interfered with the absorption of the antigen from the peritoneal cavity.
Frederick Forbert Zeit Fellow.