Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in NOD mice.
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 alpha for 22 weeks prevented the naturally occurring insulitis and diabetogenic process in NOD mice during and at least 33 weeks after cessation of IL-1 alpha treatment. Treatment with IL-1 alpha also inhibited insulitis and hyperglycemia induced by adoptive transfer of pathogenic, polyclonal CD4+8- T cells. Even after islet-cell destruction, IL-1 alpha injections in diabetic NOD mice normalized plasma glucose levels when administered in combination with insulin, whereas equivalent levels of IL-1 alpha alone did not. Our studies support the hypothesis that IL-1 alpha 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.
Formby
B
B
Sansum Medical Research Foundation, Laboratory of Immunology, Santa Barbara, CA 93105.
Jacobs
C
C
Dubuc
P
P
Shao
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000517:prevention & control*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D016219:Immunotherapy, Adoptive; D007375:Interleukin-1 / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007375:Interleukin-1