Prevention of secondary immune response with 6-mercaptopurine.

Abstract

Abstract Six-mercaptopurine (6-MP) was known to inhibit the primary immune response in rabbits when given in a dose of 6 mg. per kilogram per day and to have negligible effects on the secondary immune response. In the present study, a 25 day course of 6-MP, in this dosage, before secondary stimulation produced significant depression of antibody production to bovine serum albumin, but did not prevent the response. When the drug was given in higher doses, 12 and 15 mg. per kilogram, beginning at the time of secondary antigenic stimulation, the secondary response was regularly inhibited, with no evidence of undue toxicity from 6-MP. The findings suggest that prior failure to prevent the secondary immune response with 6-MP resulted from inadequate doses or use of inactive preparations of the drug. In a pilot study with a small number of animals it was suggested that 6-MP also interferes with the tertiary immune response. These animals had received 6-MP at the time of secondary stimulation with bovine serum albumin and had shown no antibody. The tertiary response was also deficient, although no additional 6-MP was given. Thus, 6-MP differs from such agents as total body irradiation and cortisone in suppressing at least the primary and secondary responses and perhaps interfering with immunologic memory as well.