Molecular basis for the prevention of experimental autoimmune diabetes by interleukin-1 (IL-1) inhibitors

Abstract

To investigate the role of IL-1 in nitric oxide (NO)-mediated destructive processes in the multiple low dose streptozotocin (MLD-STZ) induced model of autoimmune diabetes, CBA/H mice received 10 consecutive i.p. injections of either rat IL-1 inhibitor (IL-1 INH), or human recombinant IL-1 receptor antagonist (IL-1ra). In contrast to the control MLD-STZ group (40-45 mg/kg for 5 days) which developed persistent hyperglycemia associated with insulitis and islet cell destruction, both IL-1 INH- and rIL-1ra-treated mice were protected from the induction of the disease. Preliminary immunohistochemical studies indicated that the high local concentration of NO-producing enzyme NO synthase, present in control MLD-STZ islets, is significantly reduced in both experimental groups of mice where IL-1 activity was blocked either by IL-1 INH or rIL-1ra.