Cytotoxicity of Human <i>p</i> I 7 Interleukin-1 for Pancreatic Islets of Langerhans

TLDR

Activated mononuclear cells are key effector cells in autoimmune beta‑cell destruction that leads to type 1 diabetes. Conditioned medium from activated mononuclear cells kills rat and human islets via a picomolar IL‑1pI7 activity that is neutralized by anti‑IL‑1 antibody, whereas IL‑1pI6 and pI5 are inactive, indicating that monocyte‑derived IL‑1pI7 may contribute to beta‑cell destruction in type 1 diabetes.

Abstract

Activated mononuclear cells appear to be important effector cells in autoimmune beta cell destruction leading to insulin-dependent (type 1) diabetes mellitus. Conditioned medium from activated mononuclear cells (from human blood) is cytotoxic to isolated rat and human islets of Langerhans. This cytotoxic activity was eliminated from crude cytokine preparations by adsorption with immobilized, purified antibody to interleukin-1 (IL-1). The islet-inhibitory activity and the IL-1 activity (determined by its comitogenic effect on thymocytes) were recovered by acid wash. Purified natural IL-1 and recombinant IL-1 derived from the predominant p I 7 form of human IL-1, consistently inhibited the insulin response. The p I 6 and p I 5 forms of natural IL-1 were ineffective. Natural and recombinant IL-1 exhibited similar dose responses in their islet-inhibitory effect and their thymocyte-stimulatory activity. Concentrations of IL-1 that inhibited islet activity were in the picomolar range. Hence, monocyte-derived p I 7 IL-1 may contribute to islet cell damage and therefore to the development of insulin-dependent diabetes mellitus.