Involvement of interleukin 1 and interleukin 1 antagonist in pancreatic β-cell destruction in insulin-dependent diabetes mellitus

doi:10.1016/1043-4666(93)90003-N

Cytokine

Volume 5, Issue 3, May 1993, Pages 185-191

https://doi.org/10.1016/1043-4666(93)90003-N Get rights and content

Abstract

In this review we propose that the balance between the action of interleukin 1 (IL-1) and its natural antagonist IL-1ra on the level of the insulin-producing pancreatic β-cell may play a decisive role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We argue that IL-1 potentiated by other cytokines (tumor necrosis factor α, interferon gamma) is an important effector molecule involved in both early and late events in the immune-mediated process that leads to β-cell destruction and IDDM. We also point out that surprisingly high molar excesses of IL-1ra over IL-1 are necessary to block the action of IL-1 on islet β-cells compared to islet α-cells in vitro and in animals. We suggest that the selectivity of β-cell destruction in IDDM may be conferred on several levels: (1) homing of β-cell antigen specific T cells, (2) targeted delivery of cytokines by lymphocytic and monocytic cells to β-cells, (3) high molar excesses of IL-1ra over IL-1 needed to prevent IL-1 mediated β-cell toxicity, (4) increased β-cell sensitivity to free nitric oxide and oxygen radical formation induced by IL-1 and (5) inadequate oxidative stress response by β-cells to cytokines. Further studies are needed to establish the in vivo role of an imbalance between the amounts of IL-1 and IL-1ra produced relative to their action in the pathogenesis of IDDM.

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Review articleInvolvement of interleukin 1 and interleukin 1 antagonist in pancreatic β-cell destruction in insulin-dependent diabetes mellitus

Abstract

Blood

J Biol Chem

Kidney Intern

FEBS Lett

FEBS Lett

Biochem Biophys Res Commun

J Biol Chem

Biochem Biophys Res Commun

Immunol Today

J Autoimmunity

Genes and gene products in the development of diabetes mellitus

Cytokines and free radicals as effector molecules in the destruction of pancreatic beta cells

A role for macrophages in the pathogenesis of Type I diabetes

Autoimmunity

Murine macrophages and pancreatic beta-cells

Intercellular adhesion molecule 1 is induced on isolated endocrine islet cells by cytokines but not by reovirus infection

The autoimmune hypothesis of insulin-dependent diabetes: 1965 to the present

Cytokine gene expression in the islets of the diabetic Biobreeding/Worcester rat

J Immunol

Tumour necrosis factor alpha production is upregulated in diabetes prone BB rats

Diabetologia

Cytokines as immune effector molecules in autoimmune endocrine disease with special reference to insulin-dependent diabetes mellitus

Autoimmunity

Review article
Involvement of interleukin 1 and interleukin 1 antagonist in pancreatic β-cell destruction in insulin-dependent diabetes mellitus