Exogenous Administration of Il-Lα Inhibits Active and Adoptive Transfer Autoimmune Diabetes in Nod Mice

Abstract

Diabetes susceptibility in non-obese diabetic (NOD) mice may involve immune dysregulation resulting from cytokine deficiencies. The cytokine IL-1 plays a role in various immune as well as endocrine responses and may be hypoexpressed in NOD mice. Treatment with low levels of exogenous IL-1 a for 22 weeks prevented the naturally occurring insulitis and diabetogenic process in NOD mice during and at least 33 weeks after cessation of IL-1α treatment. Treatment with IL-1α also inhibited insulitis and hyperglycemia induced by adoptive transfer of pathogenic, polyclonal CD4⁺8⁻ T cells. Even after islet-cell destruction, IL-1α injections in diabetic NOD mice normalized plasma glucose levels when administered in combination with insulin, whereas equivalent levels of IL-1α alone did not. Our studies support the hypothesis that IL-1α suppresses autoimmune diabetes and hyperglycemia in NOD mice by pleiotropic effects on both immune and metabolic systems. Thus, IL-1 treatment could clinically be an effective immunotherapeutic modality for autoimmune diabetes mellitus by suppressing early disease progression or normalize plasma glucose levels when insulin is present.

Key Words:

• Cytokine deficiency
• systemic IL-1 treatment
• insulitis
• pathogenic
• polyclonal CD4⁺8⁻
• IL-1 pleiotropic effects.