62 PROTEIN THERAPY 



a second group, in which a leukocytosis was already present (as in 

 leukemias) the injection was followed by a decrease in the number 

 of neutrophiles. In the third group the reaction consisted chiefly 

 in an increase in the number of mononuclear elements. 



Miiller has emphasized particularly the myelocytic stimulation that 

 is brought about by milk injections. While the lymphatic apparatus 

 was practically unaffected, myelocytes were thrown into the circula- 

 tion in abundance, indicating a marked stimulation of the bone mar- 

 row. 



Recently Nagao has studied the cellular changes that follow the 

 intravenous injection of killed nonhemolytic streptococci into guinea- 

 pigs. Most of the cocci were taken up in leukocytes within five 

 or ten minutes, and cocci could be found in circulating leukocytes 

 for as long as three hours. The cocci and polymorphonuclear leu- 

 kocytes accumulate in the lungs during the first ten minutes, and it 

 is here that most of the cocci reach the interior of the phagocytes. At 

 the same time there is a general leukopenia, and the polymorphonuclear 

 leukocytes of the spleen are reduced to about one-fourth the nor- 

 mal number. There is a similar reduction of such leukocytes in the 

 bone marrow. After thirty minutes the lungs are nearly normal, 

 the number of leukocytes in the blood may be normal or increased, 

 and there is a beginning accumulation of the leukocytes in the liver 

 and spleen. There is also a marked proliferation of the endothelial 

 cells of the liver and spleen, and of the leukocytes of the bone mar- 

 row. In from two to three hours there is a marked accumulation of 

 leukocytes with ingested cocci in the liver and spleen, the number 

 of leukocytes in the blood is increased, and immature leukocytes ap- 

 pear in the blood and bone marrow, indicating an exhaustion of the 

 leukocyte- forming power of the marrow. It is suggested by Nagao 

 that the reaction of a patient to vaccine treatment may be deter- 

 mined in some degree by frequent examination of the blood, the ap- 

 pearance in it of immature leukocytes indicating danger of exhaustion 

 of leukocytogenic centers in the marrow and elsewhere. 



Cowie and Calhoun in this country made a detailed study of the 

 leukocytic reaction following intravenous typhoid injections. They 

 observed the primary leukopenia and found that the maximum re- 

 action took place between the 4th and the 9th hour after the in- 

 jection, their leukocyte counts then ranging about 30,000. The poly- 

 morphonuclear cells which appeared were new cells with large nuclei. 

 Large lymphocytes frequently disappeared at some time following the 

 injection. The small lymphocytes never wholly disappeared although 

 they were greatly decreased, in one case to 200 cells per c.mm. The 

 transitional cells were usually below normal in number while the 

 eosinophiles were not increased. They observed the appearance of 

 great numbers of myelocytes which were to be found sometimes within 



