Severe hyperglycaemia caused by autoimmunization to beta cells in rats

The non-specific activation of the immune system by administration of complete Freund's adjuvant was examined in Wistar rats as a possible means of amplification of the specific immune response directed to pancreatic B cells caused by low dose non-diabetogenic multiple injections of streptozotocin. Rats were given intraperitoneally 0.5 ml of complete Freund's adjuvant to induce polyclonal lymphocyte activation and, 1 day later, the animals were given an intraperitoneal injection of 15 mg streptozotocin/kg body weight (group 1). This combined treatment was given twice at weekly intervals. In two further groups, rats were treated with complete Freund's adjuvant alone (group 2) or streptozotocin alone (group 3) with the same doses and at the same times. Only the rats in group 1 developed delayed but severe and persistent hyperglycaemia. In addition, significant complement-dependent cytotoxicity was detected in nine out of 15 rats (60%) in group 1 in islet cells, but not in spleen lymphocytes. The pancreatic insulin content of the rats in group 1 was depleted by up to 3.1 +/- 0.5%. With these experiments, a new animal model for insulin-dependent diabetes is described; complete Freund's adjuvant/streptozotocin diabetes. In many aspects, this model of diabetes parallels the development of insulin-dependent diabetes in man, including the humoral autoimmunity to islet cell antigens.