The hypersensitiveness of the guinea pig to horse serum

The facts in this communication are related to the “Theobald Smith Phenomenon” first described by Otto. Additional observations in regard to the reaction and its pathology have been reported by Rosenau and Anderson, Besredka and Steinhardt, and Gay and Southard.

If a normal guinea pig be treated with a dose of 1/100 c.c. of normal horse serum alone, or of diphtheria antitoxic horse serum mixed with a suitable amount of diphtheria toxin, it becomes, after an interval of ten or twenty days, very susceptible to further treatment with normal horse serum. For a guinea pig whose preliminary treatment has been a toxin-antitoxin mixture, after an interval of three weeks, 5 c.c. of serum subcutaneously administered will frequently kill and will always develop symptoms. Five c.c. intraperitoneally is an almost certainly fatal dose. One one-hundredth c.c. given directly into the circulation is probably a certainly fatal dose.

As a sensitizing treatment I have employed chiefly the toxin-antitoxin mixture. As a test treatment I have administered the serum subcutaneously as a rule, but have occasionally injected serum into the circulation by the intracardiac method. Two c.c. is a safe dose for a normal animal by the latter method.

The results of other observers show that diphtheria toxin in some way increases the sensitizing power of the single small dose of serum. With serum alone the same effect can be produced by injecting fractions of the total small dose over a period of several days. In order to show the influence of the toxin, the intraperitoneal, intracerebral, and intracirculatory methods of testing must be avoided as the more vigorous reaction obtained when they are used masks the result. By injecting 2 C.C. of serum, intracardiac, into animals sensitized by toxin-antitoxin mixtures I have obtained a definite reaction on the sixth day.