Bovine islets are less susceptible than human islets to damage by human cytokines

Background The potential benefits of islet xenografting in type 1 diabetes include the intriguing, but still unanswered, possibility that the grafted xeno-islets may be less subjected to human autoimmune attack. Cytokines may play a major role in the pathogenesis of autoimmune diabetes by causing im pairment of insulin release and pancreatic islet cell toxicity. Methods. We compared insulin secretion, islet cell death and survival, indu cible nitric oxide synthase (iNOS) mRNA expression, nitrite production, and Bcl-2 and Bax mRNA expression in isolated human and large mammal (bovine) islets exposed to 50 U/ml recombinant human interleukin-1, 1000 U/ml recomb inant human tumor necrosis factor-alpha and 1000 U/ml recombinant human int erferon-gamma, Results. After 24-hr exposure, a marked decrease of glucose-stimulated insu lin secretion was observed with human, but not with bovine islets, After 48 -hr exposure, human, but not bovine, pancreatic islets showed a significant ly higher percentage of apoptotic cells compared to controls. Treatment of human islets with human cytokines induced up-regulation of iNOS mRNA, incre ased levels of nitrites, and down-regulation of Bcl-2 mRNA, with unchanged levels of Bax mRNA These parameters were not affected by cytokines in bovin e islets, Conclusions, Bovine islets are less susceptible than human islets to the ef fects of human cytokines, which may be a potential advantage of xenotranspl antation.