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Cytotoxicity of Human p I 7 Interleukin-1 for Pancreatic Islets of Langerhans
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.
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Citations
Cited by
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Metabolic reprogramming in macrophages and dendritic cells in innate immunity
Kelly, B., & O'Neill, L. A. (2015) · Cell Research · doi:10.1038/cr.2015.68 · Cited by 1,876
Interleukin-1-receptor antagonist in type 2 diabetes mellitus
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798
Self-citationThe cellular and signaling networks linking the immune system and metabolism in disease
Osborn, O., & Olefsky, J. M. (2012) · Nature Medicine · doi:10.1038/nm.2627 · Cited by 1,551
Metadata
- Authors
- Bendtzen, K., Mandrup-Poulsen, T., Nerup, J., Nielsen, J. H., Dinarello, C. A., & Svenson, M.
- Venue
- Science
- Published
- 1986-06-20
- Volume
- 232
- Issue
- 4757
- Pages
- 1545-1547
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2058455617
- Cited by
- 529
- References
- 0
- FWCI
- 23.28
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bendtzen, K., Mandrup-Poulsen, T., Nerup, J., Nielsen, J. H., Dinarello, C. A., & Svenson, M. (1986). Cytotoxicity of Human p I 7 Interleukin-1 for Pancreatic Islets of Langerhans. Science. https://doi.org/10.1126/science.3086977
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