The aim of this work was to study in vivo and in vitro the involvement of macrophages and interleukin-1beta (IL-1beta) 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. 507 +/- 81 microU/mL). In vitro, the insulin release of encapsulated islets cultured for 2 days decreased to 32 and 28%, respectively, in the presence of IL-1beta and macrophages. The addition of anti-IL-1beta antibody to the co-culture of macrophages and islets did not modify this loss of functional activity. Furthermore, IL-1beta passed through the AN69 membrane. In conclusion, macrophages are involved in damaging encapsulated pancreatic islets and are probably partly responsible for islet transplantation failure.