Cytotoxicity of peritoneal murine macrophages against encapsulated pancreatic rat islets: In vivo and in vitro studies

The aim of this work was to study in vivo and in vitro the involvement of macrophages and interleukin-1 beta (IL-1 beta) in the necrosis of encapsulated islets during xenograft and to evaluate the immunoprotective efficiency of the AN69 membrane, In vivo, 6 days after implantation, 65% of the membrane surface of the devices containing the islets was colonized with macrophages compared with only 5% of the surface of the empty control devices, The morphological aspect of implanted islets was altered and their insulin release decreased significantly compared with freshly isolated ones (265 +/- 50 vs. 501 +/- 81 mu U/mL), In vitro, the insulin release of encapsulated islets cultured for 2 days decreased to 32 and 28%, respectively, in the presence of IL-1 beta and macrophages. The addition of anti-IL-1 beta antibody to the co-culture of macrophages and islets did not modify this loss of functional activity, Furthermore, IL-1 beta passed through the AN69 membrane, In conclusion, macrophages are involved in damaging encapsulated pancreatic islets and are probably partly responsible for islet transplantation failure.