Prolongation of rat pancreatic islet allograft survival by treatment of recipient rats with monoclonal anti-interleukin-2 receptor antibody and cyclosporin.

Abstract

Since interleukin-2-receptor expressing cells play a role in allograft rejection, we investigated the effect of anti-interleukin-2 receptor monoclonal antibody treatment on graft survival of allografted pancreatic islets. When pancreatic islets obtained from Lewis A-rats (haplotype RT1a) were grafted under the kidney capsules of streptozotocin-diabetic Lewis rats (haplotype RT1u), the recipients relapsed into hyperglycaemia within 11 days (7 +/- 1 days). Treatment of the recipient rats with low-dose cyclosporin (1.5 mg/kg body weight) had no effect on allograft survival (9 +/- 1 days). The application of anti-interleukin-2 receptor monoclonal antibody (1 mg/kg body weight) for 10 days resulted in a prolongation of allograft survival (42.5 +/- 15.3, p less than 0.01). In 3 out of 11 animals a permanent normoglycaemia (greater than 120 days) associated with glucose intolerance was observed. When the recipients were treated for 10 days with cyclosporin and anti-interleukin-2 receptor monoclonal antibody, the allograft survival was also prolonged (45.1 +/- 14.6, p less than 0.01); again 3 out of 11 animals remained permanently normoglycaemic while exhibiting a normal glucose tolerance.