HYPERSENSITIYENESS, PROTEIN INTOXICATION 209 



There is, therefore, considerable evidence to show that the anaphylactic 

 shock or the repeated injections of foreign protein in animals and in man 

 are accompanied, or followed by, definite changes in some of the tissues 

 of the body. 



Protein Metabolism in Anaphylaxis. Not only have there been ob- 

 servations upon the tissue changes but a considerable number of investi- 

 gators have directed their attention to a study of the chemistry of the body, 

 to determine whether there are evidences of disturbed metabolism. With 

 the development of the theory that, the intoxication was dependent upon 

 the formation of products of protein disintegration, numerous attempts 

 have been made to demonstrate chemically the occurrence of these sub- 

 stances in the blood and tissues during anaphylactic shock. The early 

 experiments of Friedmann and Isaac, who used egg-white as antigen, 

 pointed to the fact that when doses of 5-100 c.c. were used in dogs and 

 goats, nitrogen excretion was increased in the sentitized animals as com- 

 pared to the normal controls. Schott and Heilner and Hirsch, however, 

 failed to find any increase in protein metabolism. In a more recent study 

 of this question Major has brought forward evidence to show that, 

 immediately after anaphylactic shock there is often, though not con- 

 stantly, a fall in nitrogen excretion. When rabbits are employed, these 

 animals frequently become ill 5-10 days after the intoxicating dose, and 

 during this period there is a definite increase in the nitrogen excretion, 

 at which time the animal loses weight. The loss of weight, both after acute 

 shock in rabbits and after repeated injections of foreign protein, has been 

 frequently observed, but Major considers that this is partly due to the 

 fact that the animals are likely to take less food. This fact casts some 

 doubt upon the relation which the increased nitrogen output in the urine 

 has to the previous anaphylactic shock, for it seems possible that at the 

 time the nitrogen increase appears in the urine, the animals have ex- 

 hausted their available carbohydrate and fat, and are burning their own 

 tissue proteins. 



The results of Manoiloff, however, supplied some confirmatory evi- 

 dence for the work reported by Friedmann and Isaac. Using rabbits, 

 he found that after anaphylactic shock, there was a rise in urinary 

 nitrogen, and then gradually a return to normal at the end of two to two 

 and a half weeks. Furthermore, on the basis of biological tests 

 (specific precipitin reactions) he concluded that the increase in 

 nitrogen output was not due to excretion by the kidneys of the protein 

 injected. In our laboratory this observation has been repeatedly con- 

 firmed in studying the fate of horse serum administered therapeutically 

 in lobar pneumonia and meningococcus meningitis. We have never been 

 able to demonstrate horse serum in the urine of these patients by precipita- 

 tion with immune rabbit serum. Schittenhelm and Weichardt also con- 

 firmed the results of Friedmann and Isaac, reporting an increased nitrogen 



