Successful treatment of diabetes in nod mice with advanced disease by islet isografts following immunoregulation with Linomide (quinoline-3-carboxamide)

Prevention of Diabetes in the NOD Mouse by Intra‐muscular Injection of Recombinant Adeno‐associated Virus Containing the Preproinsulin II Gene

“…I11 Furthermore, experiments in pregnant NOD mice also inhibited progression of DM, as it is well known that pregnancy is an immune-privileged state. I121 Other exogenously administered agents such as Linomide [13] and certain specific peptides [14] were also effective in preventing DM in NOD mice. Finally, introduction of gene mutations and MHC Class II genes also resulted in the prevention of DM in the NOD mice.…”

Effect of Linomide on adhesion molecules, TNF-α, nitrogen oxide, and cell adhesion

“…Firstly, lymphocytes obtained from Linomide-treated mice failed to migrate to the pancreatic islets, consequently failing to induce autoimmune insulitis and diabetes [25]. Interestingly, Linomide treatment of NOD mice with advanced diabetes that had received a syngeneic islet cell graft into the portal vein, protected them from recurrent insulitis and diabetes [25].…”

“…Firstly, lymphocytes obtained from Linomide-treated mice failed to migrate to the pancreatic islets, consequently failing to induce autoimmune insulitis and diabetes [25]. Interestingly, Linomide treatment of NOD mice with advanced diabetes that had received a syngeneic islet cell graft into the portal vein, protected them from recurrent insulitis and diabetes [25]. Secondly, monoclonal anti-CD44 antibody was shown to have a beneficial effect against autoimmune insulitis and diabetes in NOD mice, suggesting that interference in the homing of reactive T cells may prevent involvement of target organs while avoiding systemic immunosuppression [26].…”