ANAPHYLAXIS 395 



The question now arises : What is the significance of this dimi- 

 nution of alexin ? Do the animals die because of a sudden loss of 

 circulating, physiologically necessary alexin, or does the alexin take 

 an active part in producing the conditions which cause death ? 



Either of these possibilities might follow from the mere fact of 

 alexin diminution, but the former the possibility that complement 

 depletion is the cause of death was ruled out by Friedberger and 

 Hartoch. 33 They showed that, by supplying fresh complement to 

 sensitive animals at the time of reinjection, shock cannot be pre- 

 vented. They now proceeded to demonstrate the active participation 

 of complement in the production of anaphylaxis. They did this in an 

 ingenious way which depended on utilization of the fact observed by 

 Kolf, 34 Hektoen and Ruediger, 35 and others that hypertonic salt 

 solution (1.5-2 per cent.) will prevent the combination of comple- 

 ment with its sensitized cells. By slowly injecting into sensitized 

 guinea pigs 0.3 cubic centimeter of concentrated NaCI solution 

 just before the injection of antigen they were able to markedly 

 diminish anaphylactic shock saving animals from injections which 

 invariably killed the controls. 



An extremely ingenious demonstration of the important role 

 played by complement in anaphylaxis has recently been furnished by 

 Loeffler. Loeffler, 36 using guinea pigs sensitized with horse serum, 

 completely depleted their complement by injecting intraperitoneally 

 considerable quantities of sensitized sheep corpuscles. Tested by 

 injection of horse serum one hour later no anaphylaxis occurred, 

 while controls regularly succumbed. 37 



It was thus established with as much accuracy as the peculiar 

 experimental difficulties of the problem permitted that the comple- 

 ment or alexin played an important active part in the production of 

 anaphylaxis, and the next logical step was to attempt to produce the 

 anaphylactic poison by the action of alexin upon an antigen-antibody 

 complex in vitro. This was first done, with direct reference to 

 anaphylaxis, by Ulrich Friedemann. 38 Friedemann chose as his 

 antigen-antibody complex the sensitized red blood cell after he had 

 demonstrated by preliminary experiment that the basic anaphylactic 

 experiment could be carried out in rabbits with washed beef cor- 

 puscles. He found that if 3 c. c. of such corpuscles were injected 

 into rabbits and the injection repeated after 3 weeks anaphylactic 

 symptoms were regularly elicited. He then allowed alexin to act 

 upon sensitized beef blood in mtro, interrupted the action by cool- 



33 Friedberger and Hartoch. Loc. cit. 

 3 *Nolf. Ann. de Vlnst. Past., 1900. 



35 Hektoen and Ruediger. Jour. Inf. Dis., Vol. 1, 1904. 



36 Loeffler. Zeitschr. f. Immunitatsforsch^ 8, 1910. 



37 For additional evidence pointing in the same direction see also Uhlen- 

 liuth and Haendel, Zeitschr. f. Immunitatsforsch., Vol. 3, 1909. 



38 Ulrich Friedemann. Zeitschr. f. Immunitatsforsch., Vol. 2, 1909. 



