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Variation in Susceptibility to Diphtheria Toxin Among Guinea Pigs and Rabbits and Accuracy of Various Methods of Toxinantitoxin Titration

From the Bacteriological Department (K. Ando), Hygienic Institute (Director, S. Kanai) of the S. M. R. Co., Dairen, So. Manchuria

Abstract

1. The sensitiveness of the skin of guinea pigs and rabbits to a small amount of diphtheria toxin shows considerable variation locally and individually.

2. The skin of the side-chest and flank gives a uniform and more marked reaction to the injection of a small amount of diphtheria toxin than the skin of the abdomen.

3. Abnormally low skin sensitiveness to diphtheria toxin is an indication of antitoxin content in the blood serum.

4. We propose to define the term "susceptibility" as follows: Susceptibility is expressed by the M.L.D. of one toxin determined with guinea pigs of average susceptibility divided by the M.R.D. of the same toxin on the guinea pig or rabbit tested. The introduction of this idea of susceptibility would yield more accurate experimental results in regard to the assay of toxin and antitoxin.

5. Individual variation in susceptibility to diphtheria toxin among guinea pigs was considerable, and the susceptibility varied from 2000 to 75 in our tests with almost 300 guinea pigs. Normal susceptibility seems to be from 1000 to 500.
The susceptibility to diphtheria toxin of rabbits varied from 3000 to 500 in our tests with 30 rabbits.

6. Pregnancy and littering seem temporarily to reduce very much the skin sensitiveness to diphtheria toxin.

7. The M.R.D. and the Lr/500 dose of a given toxin showed considerable variation according to the varying susceptibility of the guinea pig employed for titration. The Roemer method of toxin-antitoxin titration, therefore, must be conducted as follows: the M.R.D. or the Lr/500 dose of a given toxin is determined from the ratio of the M.R.D. or the Lr/500 dose of test toxin to that of a standard toxin tested on the same guinea pig, at the same time. Male guinea pigs over 400 grams weight are preferable as test animals for the intracutaneous method.

8. By the Schick test we are enabled to discover the guinea pig of abnormal susceptibility which might cause irregularities in the result of the determination of M.L.D. of a diphtheria toxin.

9. Individual variation of susceptibility among guinea pigs might have some influence on the determination of the "Immunity index."