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Science 20 June 1986:
Vol. 232. no. 4757, pp. 1545 - 1547
DOI: 10.1126/science.3086977
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Articles

Science, Vol 232, Issue 4757, 1545-1547
Copyright © 1986 by American Association for the Advancement of Science

articles

Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans

K Bendtzen, T Mandrup-Poulsen, J Nerup, JH Nielsen, CA Dinarello, and M Svenson

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 pI 7 form of human IL-1, consistently inhibited the insulin response. The pI 6 and pI 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 pI 7 IL-1 may contribute to islet cell damage and therefore to the development of insulin-dependent diabetes mellitus.


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