Exogenous administration of IL-1 alpha inhibits active and adoptive transfer autoimmune diabetes in NOD mice. 1992

B Formby, and C Jacobs, and P Dubuc, and T Shao
Sansum Medical Research Foundation, Laboratory of Immunology, Santa Barbara, CA 93105.

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.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008297 Male Males
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001327 Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Autoimmune Disease,Disease, Autoimmune,Diseases, Autoimmune
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell
D016219 Immunotherapy, Adoptive Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314) Adoptive Cellular Immunotherapy,Adoptive Immunotherapy,CAR T-Cell Therapy,Cellular Immunotherapy, Adoptive,Chimeric Antigen Receptor Therapy,Immunotherapy, Adoptive Cellular,Adoptive Cellular Immunotherapies,Adoptive Immunotherapies,CAR T Cell Therapy,CAR T-Cell Therapies,Cellular Immunotherapies, Adoptive,Immunotherapies, Adoptive,Immunotherapies, Adoptive Cellular,T-Cell Therapies, CAR,T-Cell Therapy, CAR,Therapies, CAR T-Cell,Therapy, CAR T-Cell
D016688 Mice, Inbred NOD A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked. Non-Obese Diabetic Mice,Mice, NOD,Mouse, Inbred NOD,Mouse, NOD,Non-Obese Diabetic Mouse,Nonobese Diabetic Mice,Nonobese Diabetic Mouse,Diabetic Mice, Non-Obese,Diabetic Mice, Nonobese,Diabetic Mouse, Non-Obese,Diabetic Mouse, Nonobese,Inbred NOD Mice,Inbred NOD Mouse,Mice, Non-Obese Diabetic,Mice, Nonobese Diabetic,Mouse, Non-Obese Diabetic,Mouse, Nonobese Diabetic,NOD Mice,NOD Mice, Inbred,NOD Mouse,NOD Mouse, Inbred,Non Obese Diabetic Mice,Non Obese Diabetic Mouse

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