290 INFECTION AND RESISTANCE 



in extravascular inflammatory changes, there is none the less a 

 regular and apparently purposeful attraction or repulsion of leuko- 

 cytes evident in the circulating blood during infectious diseases. 

 That infection of the body with many micro-organisms results in the 

 increase of leukocytes, and that in others there is either no increase 

 or even a decrease, is too well known and too generally applied in 

 diagnosis and prognosis to warrant our giving up much space to a 

 review of the facts. Nevertheless, the causes which lead to a leuko- 

 cytosis in the one case, a leukopenia in the other, are still very 

 obscure and deserve discussion. 



I In the first place it is by no means certain whether a leuko- 

 cytosis signifies an active discharge of new leukocytes from the bone 

 marrow or whether it means simply an altered distribution in that 

 the phagocytes accumulated in the lymphatic and other organs are 

 attracted by chemotaxis into the peripheral circulation. Studies of 

 the bone marrow during infection as well as the occasional appear- 

 ance of myelocytes and other cells ordinarily found only in the bone 

 marrow during health would point toward a participation of active 

 bone-marrow hyperplasia in the increase of peripheral leukocytes. 

 There is no good reason to doubt, moreover, that a chemotactic stimu- 

 lus exercised in the circulation should withdraw leukocytes from 

 any place of accumulation to the circulation. Probably both proc- 

 esses take part. When bacteria are injected into the circulation of 

 an animal there is, at first, a moderate diminution of the leukocytes 

 just as there is after injection of bacteria or other substances into 

 the peritoneum. This is soon followed in most cases by a rapid and 

 progressive increase, in which, whenever the leukocytosis is one of 

 considerable degree, the polynuclear leukocytes preponderate. The 

 extensive clinical study of the white cells in infectious disease of the 

 human being give us more material for reasoning in this respect 

 than we have available from animal experiment. Infection with 

 invasive bacteria such as the pneumococcus (and Neufeld and others 

 have shown that most lobar pneumonias are accompanied by pneu- 

 mococcus bacteriemia), streptococci, staphylococci, and others is 

 always accompanied by an increase of the leukocytes, while, in 

 typhoid fever, influenzal infection, tuberculosis, and a number of 

 other infections, the leukocytes do not increase and may even de- 

 crease. How are we going to account for this ? That all these bac- 

 teria contain a substance which is positive in its chemotactic effects 

 is easily demonstrated by injecting them into the peritoneum and 

 observing an accumulation of leukocytes and a consequent phago- 

 cytosis, even in the cases of those organisms which do not call forth 

 a leukocytosis in the blood of the diseased human being. Thus it 

 has been our experience as well as that of others invariably to ob- 

 serve the rapid and complete polynuclear phagocytosis of both 

 leprosy bacilli and tubercle bacilli after injection of these micro- 



