SUCCESSFUL TREATMENT OF DIABETES IN NOD MICE WITH ADVANCED DISEASE BYISLET ISOGRAFTS FOLLOWING IMMUNOREGULATION WITH LINOMIDE (QUINOLINE-3-CARBOXAMIDE)

We have recently documented that oral Linomide (quinoline-3-carboxamid e) prevents autoimmune insulitis, islet destruction, and diabetes in N OD mice treated at an early stage (5 wk of age) of the disease. In thi s report, we show that treatment of female NOD mice with advanced dise ase (age 23-24 wk) by syngeneic islet transplantation and oral Linomid e administration results in prevention of graft insulitis and diabetes in the Linomide group up to 40 wk (diabetes at 40 wk: isograft recipi ents with Linomide n = 0 of 6; isograft recipients alone n = 5 of 6; p < 0.0001). The extent of protection from glucose intolerance by the c ombination of transplantation with Linomide was superior to that of Li nomide alone [blood glucose (mean +/- SD) 60 min post-i.p. injection o f 1 g/kg body weight glucose: Linomide plus isograft 6.7 +/- 1 mmol/L; Linomide alone 18.7 +/- 6.3 mmol/L; p < 0.0001]. Thus, Linomide shoul d be considered a potential immunoregulatory modality in patients unde rgoing pancreatic islet or whole organ transplantation. Copyright (C) 1996 Elsevier Science Inc.