CHAPTER LXXIV 

 THE TECHNIQUE OF EXPERIMENTATION IN ANAPHYLAXIS 



W. H. MANWARING 



Stanford University 



The technique of non-clinical experimentation in protein h^^persensitiveness in- 

 cludes the methods of sensitization and desensitization of laboratory animals and 

 the methods of eliciting and recording anaphylactic responses in intact animals and 

 in isolated organs and tissues from these animals, together with certain serological, 

 chemical, and physico-chemical methods particularly applicable to anaphylactic 

 study. With slight changes in detail, the methods here outlined are also applicable 

 to the study of toxin hypersensitiveness, bacterial hypersensitiveness, and other types 

 of normal and acquired hypersusceptibility. 



ACTIVE PROTEIN SENSITIZATION 



a) Guinea pigs. — Under favorable laboratory conditions 200-2 50-gm. guinea pigs 

 are readily sensitized to a sufiiciently high degree to give fatal anaphylaxis with 

 routine test doses by a single subcutaneous injection of o,oi-cc. horse serum, or an 

 equivalent amount of other protein-containing fluid. Lethal sensitization, however, 

 may develop after a smaller dose than this, e.g., after o.ooi-cc. horse serum, or even 

 after o.oooi cc. Adult guinea pigs and newborn guinea pigs are usually not sus- 

 ceptible to lethal sensitization. 



With a subcutaneous injection of o.oi-cc. horse serum, slight specific hypersus- 

 ceptibility is usually demonstrable as early as the eighth day after the injection, 

 fatal hypersensitiveness to routine test doses about the fourteenth day, and maximum 

 hypersensitiveness about the twenty-first day. After the twenty-first day, the hyper- 

 susceptibility rapidly decreases; but for at least three months it usually remains 

 sufficiently high to give fatal anaphylaxis with routine test doses. After the sixth 

 month fatal anaphylaxis usually cannot be elicited with less than two to four times the 

 routine dose. Slight kypersusceptibility to a multiple dose usually persists for the 

 lifetime of the animal and is usually transmitted to the offspring by a hypersensitive 

 mother. 



With larger sensitizing doses, e.g., o.i-cc. horse serum, lethal sensitization may 

 not develop before the twenty-first day, and maximum sensitization before the 

 fortieth to the sixtieth day.' With still larger doses, lethal sensitization may never 

 develop. 



Unsuitable food, gastro-intestinal disturbances, unfavorable climatic conditions, 

 rapid changes in temperature or in humidity, intercurrent infections, pregnancy, 

 parturition, physical injury, or the injection or ingestion of toxic substances may 

 inhibit and even completely prevent the development of lethal sensitization of guinea 



"■ Thomson, O.: Ztschr.f. Immunitdtsforsch. u. exper. Therap., 26, 213. 1917. 



989 



