THE NONSPECIFIC REACTION 59 



into a subject that is so well known and the literature of which is 

 so accessible. The discussions in Zinsser's "Infection and Resistance" 

 give a comprehensive idea of the subject. 



The experimental production of a leukocytosis, and the study of 

 the leukocytosis that is produced after the injection of a variety of 

 substances of bacterial, protein or chemical derivation have been car- 

 ried on for a considerable period and inasmuch as the results are 

 quite comparable with those obtained in the human it may be well 

 for a moment to consider the present status of our knowledge of the 

 subject. 



The effect of the injection of bacteria and bacterial extracts on the 

 leukocytes was studied experimentally by a large number of investigators. 

 Lange, injecting typhoid bacilli in rabbits, noted that after large doses 

 there was an immediate leukopenia that was later followed by a recovery 

 and a leukocytosis, in one of his cases going to 43,900. Polymorphonuclears 

 were found to predominate, with transitional and large mononuclear cells 

 appearing later. He observed the presence of normoblasts as well as 

 a polychromatophilia ; myelocytes were also noted. Goldscheider and 

 Jacob using staphylococci observed a similar reaction, although the re- 

 active leukocytosis did not reach the extreme degree that Lange found. 

 Schlesinger using streptococci could only determine a leukopenia. When 

 typhoid bacilli were used for a repeated series of injections Hirschfeld 

 found that the bone marrow became atrophic. Studer studied the effect 

 of typhoid and coli toxin on the leukocytes and Friedlander using staphylo- 

 cocci observed that with these organisms he obtained a maximum leu- 

 kocytosis with relatively no leukopenia preceding it. Samson-Himmel- 

 stjerna, one of the earlier observers, noted a leukopenia after peptone in- 

 jections. 



Andrews found that the colon bacillus produced the greatest leu- 

 kopenia in rabbits, staphylococci and diphtheroid bacilli less than colon 

 bacilli. He was of the opinion that in immunized animals there was a 

 more pronounced reactive leukocytosis than in normal animals. 



Gay and Claypole in their work on the mechanism of recovery in 

 typhoid fever reported studies which seemed to support the contention that 

 in immunized animals the leukocytic response on reinjection was greater 

 than in normal animals and that this was a specific reaction. McWilliams 

 was not able to confirm these findings. It is very probable that as a re- 

 sult of sensitization the whole organism becomes more responsive and 

 will react more readily and more intensely to a reinjection, but recent 

 work such as that of Bieling would rather indicate that to a considerable 

 degree it is immaterial what the agent is which is injected, as long as it 

 has an irritant or stimulating effect. 



Schittenhelm, Weichardt and Greisshammer went over this phase of 

 the reaction of animals to bacterial and other proteins and came to the 

 following conclusions : 



The intravenous injection of native protein, peptone and bacterial pro- 

 tein causes in the dog an immediate leukopenia depending not only on 

 the size of the dose but on the character of the agent. Native protein pro- 



