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

Summary

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 (1mg/kg body weight) for 10 days resulted in a prolongation of allograft survival (42.5±15.3,p<0.01). In 3 out of 11 animals a permanent normoglycaemia (>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<0.01); again 3 out of 11 animals remained permanently normoglycaemic while exhibiting a normal glucose tolerance.

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Hahn, H.J., Kuttler, B., Dunger, A. et al. Prolongation of rat pancreatic islet allograft survival by treatment of recipient rats with monoclonal anti-interleukin-2 receptor antibody and cyclosporin. Diabetologia 30, 44–46 (1987). https://doi.org/10.1007/BF01788907

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Key words

  • Pancreatic islet allograft
  • immunotherapy
  • anti-IL-2 RMAB
  • cyclosporin, graft histology