THE PROBABLE MECHANISM OF THE REACTION 121 



gained access to the blood stream from the lymphatics and that this 

 bacteriemia took place quite early, even before the onset of clinically 

 localizing symptoms. 



Pneumonia must be regarded, therefore, as a directly localized 

 disease and not primarily as a septicemia. 



It is the critical termination of the disease that has always in- 

 terested physicians and a number of ingenious theories have been 

 elaborated to account for the process. But as long as we sought 

 the solution of the problem along strictly immunological lines none 

 of the hypotheses put forward seemed sufficient to account for all 

 the phenomena observed. At times antibody concentration was altered 

 before or during the crisis, at other times no alteration could be 

 demonstrated. 



In more recent studies a different line of thought has been fol- 

 lowed, and it has been made probable that we must seek part of 

 the explanation in purely physicochemical alterations that seem oper- 

 ative in the mechanism of the crisis. Miiller some years ago em- 

 phasized the importance of the proteolytic enzymes of the involved 

 lung area in bringing about resolution. Later Jobling, Petersen and 

 Eggstein advanced the hypothesis that the intoxication in pneumonia 

 was of dual origin, from the invading organisms and also from 

 the autolytic products of the involved tissue and exudate. Weiss, 

 Lord and Nye have developed this same thought. According to this 

 conception recovery in pneumonia is associated with the inaugura- 

 tion of active proteolysis of the pneumonic exudate, brought about, 

 according to Lord, by an increase in the local acidity to such a de- 

 gree that the autolytic enzymes find a suitable medium for activity; 

 according to our conception, by an increase in the amount of auto- 

 lytic enzyme either from destroyed leukocytes (leukoprotease) or 

 from mobilized protease from distant organs, and associated with a 

 decrease in the antienzyme (antitrypsin), by saturation with the ex- 

 cess of protease, by increase in acidity, or by the general lowering 

 of the antitrypsin titer of the body. The whole phenomenon in its 

 sharp demarcation between profound intoxication and complete re- 

 covery resembles more closely a chemical reaction in vitro than 

 a biological reaction in vivo. In so far as we may consider the in- 

 volved tissue as being isolated from the general circulation, as Kline 

 and Winternitz have pointed out, the process must of necessity be 

 largely local in its origin and effect. Recovery must be coincident 

 not only with the destruction of the bacteria but also with the re- 

 moval of the great mass of fibrinous and cellular detritus. In all of 

 its essentials it is therefore an autolytic process and our hopes of thera- 

 peutic influence must be based not only on the idea of overcoming the 

 infecting organism but also of favorably influencing the autolytic 

 changes. The very isolation of the lung tissue from the general cir- 

 culation after the disease process has once made headway favors 



