Oral administration of Escherichia coli glutamic acid decarboxylase has immunomodulatory effects in streptozotocin-induced diabetes

The extent Of destruction of insulin-secreting beta cells of the Islets of Langerhans was investigated in an animal model using oral administration of glutamic acid decarboxylase (GAD) isolated from Escherichia coli. The extent of lymphocytic infiltration of the pancreatic Islet cells and the severity of diabetes were significantly reduced by oral administration of GAD to rats 14 days before intraperitoneal injections of streptozotocin (STZ, 40 mg/kg body wt on 5 consecutive days). In addition, oral administration of GAD to rats 14 days before or 3 days after STZ treatment significantly (P <0.05) reduced the levels of GAD-specific antibodies and improved the in vitro proliferative response of splenocytes to concanavalin A (Con A). These data demonstrate that oral GAD administration probably generates active cellular mechanisms which suppress the disease and therefore raise the possibility of using E. coli GAD as a new means for the immunomodulation of autoimmune diabetes.