Efficacy of microencapsulated islet xenografts including IL-1 receptor antagonist

Agarose microencapsulation has been proposed as a method of protecting transplanted islets against immunological attack. However, there is a possibility that some cytokines pass through the semipermiable agarose capsule and map affect on islet viability. We investigated the affect of cytokines on microencapsulated islets (MC islets) both in vitro and in a transplantation study. Purified Wistar rat islets prepared by collagenase digestion and Ficoll-conray gradient purification were enclosed in agarose capsules and cultured for six days in RPMI1640 medium with cytokines such as IL-1 beta, IFN gamma and IL-6 which were detected in a xenografted model. Not only a strong inhibition of the insulin secretion in the medium and of glucose-stimulated insulin release was observed, but also significant decrease of the amount of islet insulin were demonstrated only by MC islets cultured with 75pg/ml IL-1 beta. In contrast, the inhibitions described above were markedly improved and the amount of islet insulin increased almost up to the control level in MC islets including 7.5 mu g/ml IL-1 receptor antagonist (IL-1ra) cultured with 75pg/ml IL-1 beta. Transplantation of 500 MC islets into C57BL/6J mice with streptozotocin-induced diabetes resulted in normoglycemia for 38.7+/-10.7 days, while in the transplantation group of 500 MC islets including IL-1ra, normoglycemia was maintained for significantly longer periods (59.8+/-18.1 days). It is concluded that MC islets including IL-1ra may be suitable for xenogeneic islet rtansplantation to prolong graft survival.