Treatment of Serum Serving to Remove Its Serum-Sickness-Causing Activity

Abstract

We have reported previously concerning a reaction appearing on the ears of rabbits 1 subsequent to an injection of either whole horse serum or fractions thereof, which may be considered as analogous to serum-sickness-causing activity of the various serum proteins led to the suggestion that the more important substance concerned in causing serum-sickness may be some agent other than the proteins themselves although this agent appears to be associated with the pseudoglobulin. 3

It has been found that by the addition of adequate quantities of alkali or acid to serum (normal or immune), exposure of the mixture to heat and subsequent neutralization, the serum-sickness-causing activity may be destroyed so that rabbits injected with the customary amounts of serum will not develop manifestations of the disease.

In order to minimize or prevent damage to antibody incident to this type of treatment of serum, it is necessary to adjust the various factors concerned in the treatment of the serum. Six factors must be considered: 1, The amount of alkali used (between 0.2 gm. and 0.1 gm. for 100 cc. of serum when using NaOH); 2, the dilution of the mixture (from 1:2 to 1:10); 3, the temperature to which the mixture is exposed (from 45°C. to 55°C.); 4, the time of exposure (from 30 min. to 18 hr.); 5, the type of antibody in the serum; 6, the particular sample of serum being treated. The first 4 factors must be balanced against each other in relation to the last 2 factors.

By this method the serum-sickness-causing factor may be destroyed so that rabbits receiving treated serum (10 cc. per kg.) do not develop serum-sickness while rabbits injected with the same untreated serum develop manifestations of serum-sickness in 6 of 10 animals. In sera which are no longer active in causing serum-sickness, from 50% to 100% of the original protective antibody is retained.