Propranolol: An effective immunosuppressive agent in rat heart-lung transplantation

We have demonstrated that propranolol administration substantially increases allograft survival following rat heart-lung transplantation. Graft rejection appears to result from a T lymphocyte-initiated proliferative response, and propranolol has been shown to inhibit in vitro mitogen-induced T lymphocyte transformation. This is the first report describing the apparent in vivo immunosuppressive activity of propranolol. Clinical transplant rejection is currently treated with relatively toxic drugs including azathioprine and corticosteroids. Propranolol has proved to be free from major toxic effects. We found that low-dose propranolol (1 mg/kg/day) extended heart-lung allograft survival from 6 to more than 12 days when administered as a single agent. Higher propranolol doses (2 and 5 mg/kg/day) also increased graft survival, but to a lesser extent. Further, low-dose propranolol combined with azathioprine (30 mg/kg/day) and methylprednisolone (5 mg/kg/day) resulted in allograft viability in certain rats for longer than 50 days. This 8-fold increase in survival time is particularly remarkable in light of the 75% reduction in concomitant corticosteroid administration in these rats. A comparable decrease in the amount of steroids used to inhibit rejection in clinical transplant patients should result in markedly diminished steroid toxicity. These data suggest that low-dose propranolol is an effective immunosuppressant in the rat heart-lung allograft model, and that utilization of low-dose propranolol could be important in controlling transplant rejection in humans.