In vivo Suppression of Allograft Rejection by Cyclic AMP Increasing Agents

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Abstract
This study was undertaken to elucidate the possibilities of modulating the survival of allogeneic tissue grafts by administration of cyclic AMP-increasing agents to the graft recipients. Heterotopic grafting of split mouse hearts across a strong H-2 barrier was used. It was found that Vibrio cholerae enterotoxin, which activates adenylate cyclase in mammalian cells, gave a marked prolongation of the graft survival time when given shortly before (but not after) transplantation. Also the administration of a combination of cyclic AMP and theophylline prior to or around transplantation increased graft survival time significantly. In contrast, no effect was obtained with choleragenoid, a membrane-binding cholera toxin analogue devoid of cyclic AMP-increasing activity.