Our experiments have shown definitely that guinea pigs, once injected with sublethal doses of bacterial proteotoxins (anaphylatoxins), acquire distinct tolerance to these poisons. The degree to which such resistance or tolerance is developed is never very high, in no case in our experiments exceeding the ability to withstand one and one half to twice the fatal dose of the poisons. During the three or four days immediately following the first injection the animals appear to be slightly less resistant than are normal controls, this depending probably upon the in jury done by the administered poison. Tolerance begins to be evident after from four to seven days, seems to be most highly developed in about two weeks, but lasts in a diminishing degree for at least as long as sixty days.
Our experience, in this respect, with the poisons resulting from the contact of active serum and bacteria is similar to that of Vaughan with the toxic protein split products obtained by chemical methods.
The development of increased resistance definitely established, the questions immediately arise: (1) Is this tolerance specific? And (2) can it be passively transferred, with the serum, to a normal animal? We have begun to seek answers for these problems but as yet our data are too meager to permit definite conclusions.
The significance of the existence of higher resistance in animals treated with proteotoxins is far reaching both in connection with anaphylaxis and with immunity in general. We are not inclined to attribute to it as predominant a part in anti-anaphylaxis as is assigned to it by Bessau. For, in the first place, tolerance to the poisons is never developed to a very high degree, and, moreover, it does not become evident until three or four days after the first injection, while anti-anaphylaxis develops almost immediately after shock. However, there seems to us to be strong presumptive evidence that such tolerance to the poisons may play an important and, possibly, a non-specific part in anti-anaphylaxis, the chief underlying and specific cause of this phenomenon being the exhaustion of antibodies, or desensitization in the sense of Besredka.
The relation of such tolerance to the resistance of the animal to bacterial infection is, of course, obvious if we accept the possibility of the production of such poisons in the injected body and their participation in the production of bacterial toxemia. We hope to throw more light on these relations in another paper dealing with the aggressin-like properties of the proteotoxins.