310 LOCAL TLSSUE REACTIVITY 



exotoxin-pioducers, as ior exanij^lc, B. dysenteriae, Streptococcus 

 licniolyticiis scarldtnuw, J'ibiio cholerae, and possibly others. It is 

 necessary, howexer, to leave the question open as yet xvhether the 

 active principles are identical with these true exotoxins or should 

 be considered as independent substances closely allied to the true 

 exotoxins in nature and ininuuiological behaxior. 



RELATION OF THE ACTIVE PRINCIPLES OF THE 

 PHENOMENON TO ENDOTOXINS 



Pfeiffer xvas responsible for the conception of endotoxins as 

 poisons held in the bacterial cells until they have disintegrated. 

 The endotoxins xvhich appeared bound xvith the bacterial proto- 

 plasm Avere extracted from the bacterial cells by autolysis, drying, 

 application of various chemical reagents and other methods, the 

 description of xvhich does not belong to the scope of this mono- 

 graph. The endotoxins obtained from a large variety of micro- 

 organisms {B. coll, B. paratypJwsus, B. typhosus, B. dysenteriae, 

 the hemogiobinophilic group; meningococcus, gonococcus, etc.) 

 were irregularly toxic to laboratory animals, the dose appar- 

 ently bearing little relation to the effect. Vaughan demonstrated 

 that all proteins, bacterial or otherxvise, yield upon hydrolysis with 

 alkalinized alcohol, toxic split products which possess many of the 

 properties of endotoxins. The symptoms obtained by intravenous 

 injection of the toxic substances under discussion (similar to those 

 described below) and the pathological findings, appear to be the 

 same with various microorganisms. The main distinction between 

 the endotoxins and true exotoxins lies in their lack of neutraliz- 

 ability by means of immune sera. Pfeiffer and Bessau (1910, 1912) 

 demonstrated that although a certain amount of inactivation of 

 toxic substances through addition of sera may be observed, the 

 imminie sera have no superior neutralizing properties over nor- 

 mal sera and there is no neutralization in "multiple proportions" 

 similar to the diphtheria toxin+antitoxin reaction. Thus, if a 

 certain amount of endotoxin is inactivated by a given amount 

 of serum, multiples of the endotoxin cannot be neutralized even 

 with very large amotnits of serum. The review of the work dealing 

 with neutralization of endotoxins suggests that the question may 

 be best left open. In view of the extreme irregularity of the 

 lethal effect upon laboratory animals, in many instances, especially 

 in those xvhere work was done on a limited ntmiber of animals, no 

 conclusion could be drawn whether neutralization was obtained 



