Increased sensitivity to anaphylactic shock in guinea pigs induced by prolonged treatment with epinephrine prior to challenge

Abstract

In the first of two experiments concerned with studies of epinephrine tolerance, guinea pigs were divided into a control and an experimental group. Each animal was sensitized by an injection into a pad of each hind foot with a volume of 0.1 ml. which contained crystalline bovine serum albumin (BSA) dissolved in saline and emulsified with complete Freund adjuvant. All animals were challenged 21 days later by an intravenous injection with 8 mg. BSA dissolved in 0.5 ml. saline. Each control animal was given a daily injection of saline beginning the day of sensitization and continued until challenge. Each animal in the experimental group was given a daily intraperitoneal injection of 0.08 mg. epinephrine beginning the day of sensitization and continued until the day of challenge. The control group showed a mortality rate of 73 per cent. The fact that epinephrine pretreatment failed to afford protection against anaphylactic shock was demonstrated by the high mortality rate of 85 per cent in the experimental group. In the second experiment, guinea pigs were divided into control and experimental groups and treated as in the first experiment; however, both groups were given 10 μg of epinephrine with the challenging dose of antigen. Epinephrine protected the control group from shock when given at challenge, as shown by the resulting mortality rate of only 27 per cent. Epinephrine showed much less protection when given at challenge to the group which had been pretreated with the hormone as shown by the mortality rate of 67 per cent in the latter group. The above studies demonstrated that guinea pigs develop tolerance to epinephrine when it is given over a period of time prior to challenge for anaphylactic shock, which renders them unprotected by epinephrine administered intravenously at the time of challenge.