206 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



There can be no doubt that the evidence which has been brought for- 

 ward is sufficient to demonstrate clearly that an important part of the 

 reaction during anaphylactic shock is intracellular in nature and is de- 

 pendent upon the formation of some toxic substance or reaction in the 

 body cells and especially the smooth muscle cells. 



But whether this is the only method by which the intoxication takes 

 place is still questioned by the adherents of the humoral theory. The 

 striking resemblance between the anaphylactic shock and the intoxication 

 produced by the injection of certain protein derivatives formed originally 

 the basis for the humoral theory of the nature of anaphylactic shock. The 

 early demonstration of de Waele and Biedl and Kraus that products of 

 protein digestion, such as peptone and products of proteolysis, produce 

 effects in animals very similar to anaphylactic shock, led to an enormous 

 amount of work in an attempt to demonstrate that such products were 

 formed by splitting of protein in the blood of the animal during anaphy- 

 lactic shock and resulted in the typical intoxication. The work of 

 Vaughan showing that such substances might be obtained from bacteria by 

 proteolysis, and the demonstration by Friedberger(&) of so-called ana- 

 phylatoxin which could be produced outside the body by the digestion of 

 serum and the bodies of bacteria, both led to the support of this hypothesis. 

 In general three hypotheses as to the formation of these toxic substances in 

 the blood have been advanced and have formed the basis of much experi- 

 mentation, though all depend for their explanation of the phenomenon upon 

 the assumption that a union takes place between the circulating antigen and 

 antibody, with the formation of a toxic substance either from the antigen 

 or from the body fluids of the animal. The theory advanced by Jobling, 

 Peterson and Eggstein(a) assumes that the union of antibody and antigen 

 removes the antitryptic factor in the blood, releases the tryptic ferment, 

 and thereby initiates cleavage of the blood proteins and the production of 

 toxic substances. Another theory which has been brought forward and 

 been the subject of an extremely interesting series of experiments by 

 Novy and De Kruif regards the union of the antigen and antibodies as 

 disturbing the delicate equilibrium of the plasma colloids which initiate 

 changes that allow the blood to become toxic. 



There are innumerable experiments which go to show that the serum 

 of animals may be rendered toxic either for the same species or for 

 different species by a great variety of manipulations. Thus, incubation 

 of a normal serum with a specific precipitate formed by the interaction of 

 precipitin and precipitinogen results in the formation of a toxic substance 

 (anaphylatoxin). In the same way, normal serum incubated with an 

 emulsion of living or dead bacteria or with such inanimate substances as 

 kiesselguhr with kaolin or with the sols of agar-agar, with heat-coagulated 

 protein or even by shaking with chloroform will render it toxic. In the 

 experiments of Novy and De Kruif the toxicity of the serum often ap- 



