EXPERIMENTS ON THE PRODUCTION OF SPECIFIC ANTISERA FOR INFECTIONS OF UNKNOWN CAUSE : III. THE EFFECTS OF A SERUM PRECIPITIN ON ANIMALS OF THE SPECIES FURNISHING THE PRECIPITINOGEN.
There is present in serum of high precipitin titer, produced by the repeated injection of rabbits with the blood-free serum of guinea pigs or dogs, a principle highly toxic for animals of the species furnishing the antigen. Intravenously the serum causes severe shock, and even sudden death, while locally it gives rise to acute inflammatory changes and profuse capillary hemorrhages. The complete removal of hemolysins and hemagglutinins from the serum by exposing it repeatedly to washed red cells lessens its toxicity to only a slight degree and one obviously dependent on these elements; while the further removal of precipitin by specific precipitation in vitro has no detoxifying effect whatever. Whether the toxic principle is a hitherto unrecognized antibody or perhaps a toxic product of the interaction of precipitin and precipitinogen,-one formed as readily in the test-tube as in the animal body,-remains to be determined. The symptoms of guinea pigs and dogs given an intravenous injection of treated or untreated serum markedly resemble those of anaphylaxis, but our attempts at desensitization have been unsuccessful. The local lesion in guinea pigs is more severe than that of the Arthus phenomenon. But these differences from anaphylaxis may, of course, be dependent merely on differing proportions of constituents that are themselves, as yet, scarcely apprehended. Our observations, as here summed up, were made with a practical point in mind, and as regards this point they are of a discouraging nature. In papers already published it has been shown that sera specifically effective against infections of which the excitant is unknown can in some cases be obtained by using infected tissue itself as antigen. Such sera must, of course, be deprived of antibodies injurious to tissue, prior to their employment in the animal body; and this was successfully accomplished in our early experiments by exhaustion with washed red cells. The purpose of the present work was to determine whether serum used as antigen gives rise to injurious principles in the antiserum. For the serum of infected individuals would in many diseases form a convenient antigen. It is evident that injurious principles result from its use, and that they are not removed from the antiserum when the latter is exhausted with red cells and its precipitin removed by specific precipitation, nor can their action be nullified by desensitization as carried out in anaphylaxis. Unless the obstacle of their presence is in some way overcome the body fluids of infected human beings cannot be practically utilized for the production of antiserum. In test animals the difficulty is not so grave. For we have found that the toxic antiserum produces no enduring lesions when it is administered intravenously in non-lethal doses.
Laboratories of The Rockefeller Institute for Medical Research.
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Rous
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Wilson
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Oliver