FAILURE OF 6-MERCAPTOPURINE TO PROLONG THE SURVIVAL OF SKIN ALLOGRAFTS IN MICE

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Abstract
Three models, using different strains of inbred mice, were employed with the idea of progressively weakening the histocompatibility differences in order to unmask any suppressant action of 6-mercaptopurine (6-MP) on cell-mediated immunity, as judged by the prolongation of skin allograft survival. They were: (1) The H-2-incompatible model, where the strains were C57BL/10ScSnJ males (H-2b) as the donors and AKR/J males (H-2k) as recipients. (2) The H-2-compatible model, using C3H/HeJ males (H-2k) as donors and AKR/J males (H-2k) as recipients. (3) The congenic resistant pair models, where the strains used were similar at all known histocompatibility loci except probably two. In the first model, the congenic resistant strain B10LP was used as recipients, and the donors were the inbred partner strain, C57BL/ScSnJ. These differ at the H-S and probably the H-13 histocompatibility loci. In the second and weaker model, the congenic resistant strain “cinnamon” was used as donors and the inbred partner strain, the strong A, served as the recipients. These differ at the H-1 and H-3 histocompatibility loci. The results showed that 6-MP, given in two dosage schemes, a short intensive course of 50 mg/kg i.p. from day 0 to day 5, and a more prolonged course of 15 mg/kg i.p. daily from day −1 to day 14, and then if necessary thrice weekly until rejection, did not prolong the survival of skin allografts, even in the congenic resistant pair with the weakest histocompatibility differences. Thus, it was concluded that 6-MP had little or no effect on cell-mediated immunity in the mouse, and it is postulated that in this species 6-MP selectively depresses humoral antibody production.

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