I092 NON-SPECIFIC PROTEIN THERAPY 



promptly with an increase in antibody titer, variations occurring according to the agent used 

 for stimulation and the particular antibody under investigation. Freund and Dresel have 

 noted the appearance of anthracocidal substances.' 



Increase in protection against infection has been noted ever since the early experiments 

 of Pfeiffer^ who studied the effect of non-specific injections on the resistance of guinea pigs to 

 cholera.3^ This protection may be effective to approximately ten times the lethal dose, but 

 is of transient character. The incubation time of injections, in humans at least, may be pro- 

 longed.' There is, on the other hand, no clear-cut evidence that non-specific reactions, if 

 initiated at the time of an intoxication or after an intoxication has been established, are in 

 any manner anlitoxic}'^° It is true that if the animal has been treated before the injection of 

 the toxin (tetanus, diphtheria, ricin, etc.), some evidence for an increase in resistance may 

 be found, but the action is uncertain and erratic. 



If we turn now from the consideration of the fluid constituents of the blood to the walls 

 of the capillaries we observe one of the most important tissues in which non-specific reactions 

 take place. And in this connection it is practically impossible to divorce consideration of the 

 autonomic nervous influences, ionic and hormonic changes, and the anatomical peculiarities 

 of the system. From the latter aspect alone we must consider as separate entities the reticulo- 

 endothelial system;""'^ the endothelium of the splanchnic area (particularly that of the liver, 

 spleen, kidneys, etc.) which is anatomically adopted as a filtering mechanism par excellence 

 (Zimmermann) ^'^ and is, in addition, located in organs that normaUy are functionally very active ; 

 and, finally, the ordinary vascular endothelium and the specialized endothelium of the blood 

 and leukocyte-forming tissues. In all cases stimulation is associated with an increased per- 

 meability, and this is followed either by a rapid (normal) or slow (fatigue) return to a normal 

 status, which may be overaccentuated. With certain agents (the metallic poisons, etc.) an 

 increased density of the membrane surfaces may become apparent with a diminution of 

 permeability. If severe enough this may, of course, lead to the death of the cell. [For general 

 orientation the monographs of Osterhout,'s Lillie,'* and Hoeber'' should be consulted.] The 



• Freund, H., and Dresel, E. G.: Arch.f. exp. Path, und Pharm., 91, 317. 1921. 

 ^Pfeiffer, R., and Isaeff: Zeit.f. Hyg., 16, 282 and 287. 1894. 

 sKepinow, L.: Camp. rend, de la Soc. Biol., 91, 244. Parib, 1924. 

 4 Harvey, W. F., and Iyengar, K. R.: Jour. Med. Res., 9, 737. 1922. 

 sBechhold, H.: Miinch. med. Wchr., 69, 1447. 1922. 

 6 Wolff-Eisner, A.: Kl. Wchr., 6, 545. 1927. 



7 Weichbrodt, R.: Dent. med. Wchr., 51, 1949. 1925. 



8 Wolfi-Eisner, A.: loc. cit.; Hoefer, P. A., and Herzfeld, E.: Arch. f. e.xp. Path, und Pliarm., 



99, 380- 1923- 



9 Herzfeld, E., Meyer-Umhofer, P. and Becker: Deut. med. Wchr., 52, 1464. 1926. 



"" Weichardt, W.: Miinch. med. Wchr., 67, 1085. 1920. 



" Busson, B.: loc. cit.; Aschoff, L.: Lectures on Pathology. New York: Paul B. Hoeber, 1924. 



" Saxl, P.: Fortschritte und Prohleme in der Therapie, innerere Krankheilen. Berlin: Springer, 

 1926; and Wien. Arch. inn. Med., 13, 7. 1926. 



"Mattausch, F.: Med. Kl., 20, 240, 277. 1924. 



"1 Zimmermann, K. W.: Der feinere Bau der Blutkapillaren. Miinchen und Berlin: Bergmann and 

 Springer, 1923. 



'5 Osterhout, \V. J. v.: Injury, Recovery and Death. Philadelphia and London : Lippincott, 1922. 



'^ Lillie, R. S.: Protoplasmic Action and Nervous Action. Chicago: University of Chicago Press, 

 1923- 



■7 Hoeber, R.: Physikalische Chemie der Zelle und Geicehe (5th ed.). Leipzig, 1922. 



