Effect of 6-Mercaptopurine (6-Mp) on Different Classes of Antibody

Abstract

M a n y antigens have been found to induce the formation of several molecular classes of antibodies. Under most circumstances, the first antibody to be synthesized in response to antigenic stimulation is a 19S ('yM) globulin, while 7S immunoglobulins (3'G) appear somewhat later. The factors controlling the synthesis of these 2 proteins are poorly understood. The recent report of the selective suppression of "),G-antibodies in rabbits by 6-mercaptopurine (6-MP) suggests that the formation of each of these immunoglobulins is controlled by a separate mechanism (1). Furthermore, 19S antibody synthesis in m a n appears more resistant to 6-MP treatment than 7S antibody formation (2, 3). I n the present paper the effect on 7 M -and "~,G-antibody formation of 6-MP has been further investigated in the primary and secondary response of mice and rabbits. Materials and MethodsAnimals.--White Swiss mice of both sexes weighing 25 to 30 gm and white outbred male or female rabbits weighing 3.5 to 4.5 kg were used.Immunization.--Rat erythrocytes were obtained by cardiac puncture from Wistar albino rats and washed 3 times with buffered (pH 7) saline. Twenty groups of 10 mice were immunized with an intravenous dose of 0.25 ml of a 50 per cent suspension of rat erythrocytes (large dose). Sixteen groups of 10 mice were immunized with an intravenous injection of a 2.5 per cent suspension of rat erythrocytes (small dose). A second injection of the same dose of rat erythrocytes for the appropriate group was given either 2 or 3 weeks later in order to study the anamnestic response. Twelve rabbits were injected intravenously with 1 ml of a 50 per cent saline suspension of human type A erythrocytes washed 3 times. A similar injection was given 20 days later.Administration of 1 was brought into solution in distilled water with the minimal amount of NaOH necessary to dissolve the drug. Eight groups of 10 mice were treated daffy with 50 mg/kg/body weight intraperitoneally for the first 10 days of the immunization. Ten groups of mice were given 150 mg/kg/body weight intraperitoneaUy for 4 days beginning on the day of the second injection. Six rabbits received two 10-day courses of 6-MP (6 mg/kg) beginning on the day of each antigen injection.

The Immune Response to Sheep Erythrocytes in the Mouse

“…It may be speculated that 19S activity ceases as 7S antibody is formed. The prolongation of 19S antibody synthesis by the inhibition of 7S antibody formation after administration of 6-mercaptopurine favors this view (30). Moreover, the presence of a lag period of 40-50 hr for the inhibition of 19S antibody formation by passively administered antibody (31) may be compatible with the timing of the latent period for 7S antibody activity and the peak of 19S antibody activity demonstrated in the present work, ff we assume that the newly formed antibodies are retained in higher concentration in lymphoid tissue for which some evidence is available (32).…”

Immunologic responses to bacteriophage ϕX 174 in immunodeficiency diseases

“…Our study is primarily concerned with large differences in antibody concentrations, and the results would not be changed significantly by using other methods of calculation. (25,26), and L-aspariginase (27) have been shown to suppress the IgG antibody response to a much greater extent than the IgM antibody response. In adult rabbits, 6-mercaptopurine impairs mainly the IgG response; in young rabbits, however, both IgG and IgM antibody responses are suppressed (28).…”

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

“…A dose of bovine -globulin (BGG) insufficient to elicit an antibody response in rabbits induced lgM and lgG responses when given after a one-week course of low doses of 6MP. Treatment with a lower dose of 6MP inhibited selectively the production of lgG antibodies while that of lgM antibodies persisted for many weeks [220]. Treatment with a lower dose of 6MP inhibited selectively the production of lgG antibodies while that of lgM antibodies persisted for many weeks [220].…”