Effect of azathioprine and prednisolone on passive enhancement of rat renal allografts.
Passive enhancement provides only partial suppression of rejection in the (DA X Lewis)F1 to Lewis renal allograft model. Suboptimal (8 mg/kg/day) and supraoptimal (30 mg/kg/day) doses of azathioprine administered with enhancing serum failed to suppress the rejection reaction in enhanced animals. Similarly, suboptimal (4 mg/kg/day) and optimal (16 mg/kg/day) doses of methylprednisolone were ineffective. However, the onset of rejection in enhanced animals was delayed by the use of both azathioprine (30 mg/kg/day) and methylprednisolone (16 mg/kg/day). The survival times of enhanced animals treated with azathioprine were significantly shorter than those of animals treated with enhancing serum alone, suggesting that this agent may prevent the development of autoenhancement. Although suboptimal doses of antilymphocyte serum suppress rejection in this enhancement model, the dose requirements of conventional immunosuppressive agents appear to be maximal rather than minimal.