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

Cytokine. 1993 May;5(3):185-91. doi: 10.1016/1043-4666(93)90003-n.

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 beta-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 alpha, interferon gamma) is an important effector molecule involved in both early and late events in the immune-mediated process that leads to beta-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 beta-cells compared to islet alpha-cells in vitro and in animals. We suggest that the selectivity of beta-cell destruction in IDDM may be conferred on several levels: (1) homing of beta-cell antigen specific T cells, (2) targeted delivery of cytokines by lymphocytic and monocytic cells beta-cells, (3) high molar excesses of IL-1ra over IL-1 needed to prevent IL-1 mediated beta-cell toxicity, (4) increased beta-cell sensitivity to free nitric oxide and oxygen radical formation induced by IL-1 and (5) inadequate oxidative stress response by beta-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.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / pathology*
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / physiology*
  • Interleukin-1 / toxicity
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology*
  • Sialoglycoproteins / physiology*
  • Sialoglycoproteins / toxicity

Substances

  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins