60 PROTEIN THERAPY 



duces such a leukopenia only after sensitization, peptone with the first 

 injection. Among the bacterial agents the typhoid bacillus when injected 

 produces the most persistent leukopenia ; some varieties of tuberculin, colon 

 bacilli and staphylococci also have the same effect. On reinjection the 

 leukopenia becomes less marked in degree and duration. The authors sug- 

 gest that this effect is due to a functional paralysis or depression of the 

 bone marrow. It is probable that in a great part the peripheral leukopenia 

 so observed is due to the accumulation of the leukocytes in the internal 

 organs spleen, liver, etc. If the injected dose is too large the animal 

 of course dies in this shock or depression stage. 



The stage of leukopenia is followed by one of leukocytosis which per- 

 sists for from three to six days ; the degree of the reaction is diminished on 

 further injections. Of the bacterial injections typhoid and staphylococci 

 produce the most marked leukocytosis. 



This reactive leukocytosis that follows is of myeloid type that is, of 

 neutrophile polymorphonuclears, large mononuclears and transitional types. 

 Eosinophils are at times also increased. The lymphatic apparatus is rela- 

 tively passive. 



The protein split products and the bacterial proteins also stimulate the 

 hematopoietic system, as indicated by the appearance of normoblasts, meg- 

 aloblasts and polychromatic reds in the days following the injection. 



Two or more factors enter into these changes that have been observed 

 in the relation of the leukocytes after nonspecific injections. The leuko- 

 penia that follows immediately is due to an accumulation of the leukocytes 

 in the internal organs lungs, spleen, liver, gastrointestinal tract and the 

 bone marrow. Dale is inclined to the belief that because of changes in 

 the intima of the capillaries and smaller vessels the leukocytes tend to 

 adhere to the walls and therefore do not appear in the circulating blood. 

 The leukocytosis that follows the leukopenia is a reactive phenomenon due 

 to a stimulation of the bone marrow. Andrews followed the Arneth count 

 and found that the neutrophils with undivided nuclei outnumbered the 

 divided ones. The presence of bone marrow cells of various types after the 

 reaction was further evidence of the stimulation of the marrow. 



During the height of the reaction the leukocytes are more actively 

 phagocytic than normally, the ingestion of erythrocytes by the polymorpho- 

 nuclear leukocytes being observed after typhoid injection. 



That a leukocytosis followed the subcutaneous injection of nu- 

 cleins was noted when they were introduced about thirty years ago; 

 Bauer studied the leukocytosis that followed the fixation abscess 

 and a similar reaction on the part of the leukocytes was observed to 

 some degree after serum injections, after the intravenous injection 

 of colloidal metals, following autoserotherapy, etc. 



With the development of nonspecific therapy and the endeavor 

 to find a satisfactory theoretical basis for the therapeutic results 

 obtained, a number of investigators naturally turned to the study 

 of the leukocytic reaction and its possible bearing on the problem. 

 Some believe that the chief factor in the therapeutic result lies in 

 the leukocytic stimulation, others see merely an accessory factor in 



