Comparison of suppressive potency between azathioprine and 6-mercaptopurine against mitogen-induced blastogenesis of human peripheral blood mononuclear cells in-vitro.

Azathioprine (AZ) is a prodrug of 6-mercaptopurine (6-MP), but little is known about the relative suppressive efficacy of these agents against blastogenesis of human peripheral blood mononuclear cells (PBMCs) in-vitro. We compared the pharmacological efficacy of AZ and 6-MP against T cell mitogen-induced blastogenesis of PBMCs in-vitro. PBMCs were obtained from seven healthy subjects. The potency of AZ and 6-MP to suppress PBMC-blastogenesis in-vitro was compared using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay procedures. Production of 6-MP from AZ in PBMC culture was examined by high-performance liquid chromatography. Both AZ and 6-MP dose-dependently suppressed PBMC blastogenesis. Mean +/- s.d. IC50 (concentration of drug that gave 50% inhibition) values for AZ and 6-MP were 230.4 +/- 231.3 and 149.5 +/- 124.9 nM, respectively. Thus, the potencies of AZ and 6-MP to suppress PBMC blastogenesis were not significantly different. A significant correlation was observed between the IC50 values of AZ and 6-MP (P < 0.01, n = 6). After incubation of PBMCs with 100 microM AZ for 4 days, 35.3-92.5 microM 6-MP was liberated into the culture medium. The ratio of 6-MP liberation from AZ was influenced by the presence of PBMCs, but not by the medium or fetal bovine serum. The results suggest that the suppressive potency of the prodrug AZ and its converted form 6-MP against blastogenesis of human PBMCs in-vitro is similar, although PBMCs appeared to convert AZ to 6-MP. AZ is suggested to be effective after conversion to 6-MP to express immunosuppressive efficacy in-vitro.