990 TECHNIQUE OF EXPERIMENTATION IN ANAPHYLAXIS 



pigs,^ Among the more important inhibiting substances are foreign serum, autolytic 

 tissue products, and peptone. An increase in the sensitizing dose and a prolongation 

 of the incubation period will at times ovecome the handicap from unfavorable factors. 



b) Rabbits. — Adult rabbits are readily sensitized sufiEiciently to give recordable 

 anaphylactic reactions, but fatal hypersensitiveness is rarely acquired by full-grown 

 rabbits. Young rabbits (750-900 gm.) occasionally acquire lethal hypersensitiveness 

 following a single subcutaneous injection with 3-5-cc. horse serum, or an equivalent 

 amount of other protein-containing fluid. A higher percentage of lethal sensitization 

 is obtained with multiple injections. Auer,^ for example, made four to eight sub- 

 cutaneous, intraperitoneal or intravenous injections of 3-5-cc. horse serum, at five- 

 to six-day intervals, and tested his animals from four to six weeks after the final 

 sensitizing dose. Drinker and Bronfenbrenner^ used daily intravenous injections of 

 0.5-cc. sheep serum, in three periods of from three to five days each, with a two- to 

 three-day interval between periods, and tested their animals from ten to fourteen 

 days after the final sensitizing dose. Probably the most dependable method is the 

 method indorsed by Coca,^ daily or periodic injections controlled by the precipitin 

 titre, maximum sensitization in rabbits being apparently synchronous with a pre- 

 cipitin titre of 1 : 6,000 in the rabbit's serum. 



Unfavorable food, unsuitable temperature, excessive humidity, pregnancy, inter- 

 current infections, etc., may inhibit or even completely prevent the development of 

 lethal hypersensitiveness in rabbits. 



c) Dogs. — Dogs may be sensitized sufficiently to give recordable anaphylactic 

 reactions by a single subcutaneous injection of 0.3-0. 5-cc. horse serum per kilogram 

 of body weight. Hypersensitiveness, however, usually develops in but two-thirds of 

 the dogs so injected. A higher percentage of sensitization is conferred by Weil's 

 method,^ a single subcutaneous injection of 0.3-0.5 -cc. horse serum per kilogram of 

 body weight, followed twenty- four hours later by an intravenous injection with the 

 same dose. About 95 per cent of the dogs so injected become demonstrably hyper- 

 sensitive, about one-quarter of them sufficiently so as to give lethal anaphylaxis with 

 routine test doses. The height of the sensitization in dogs is apparently reached 

 about the eighteenth to the twenty-first day. After the twenty-fourth day, sensitiza- 

 tion gradually decreases. By the seventh week, fully two- thirds of the dogs are com- 

 pletely desensitized. 



With certain protein-containing fluids, however, dogs are less readily sensitized. 

 With the same sensitizing doses of goat serum, for example, only about a third of 

 the dogs become hypersensitive, and with equivalent doses of egg white, demon- 

 strable sensitization does not take place.^ 



' Wells, H. G.: Physiol. Rev., i, 44. 1921; Longcope, W. T.: ibid., 3, 240. 1923. 



' Auer, J.: J. Exper. Med., 14, 476. 191 1. 

 """3 Drinker, C. K., and Bronfenbrenner, J.: J . rminunoL, 9, 397. 1924. 



^ Coca, A. F.: Essentials of Immunology, pp. 153, 155. 1925. 



s Weil, R.: /. Immunol., 2, 525. 191 7. 



''Manwaring, W. H., Marino, H. D., McCleave, T. C, and Boone, T. H.: Proc. Soc. Exper. 

 Biol. &• Med., 24, 650. 1927. 



