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PMID: 20173777 Published · ppublish English Journal Article Review

Blockade of interleukin 1 in type 1 diabetes mellitus.

Nature reviews. Endocrinology ·Vol. 6 ·No. 3 ·2010-03-00 ·Pages 158-66

Mandrup-Poulsen T, Pickersgill L, Donath MY

Abstract

Interleukin 1 (IL-1) is a 17 kDa protein highly conserved through evolution and is a key mediator of inflammation, fever and the acute-phase response. IL-1 has important functions in the innate immune defense against microbes, trauma and stress, and is also an effector molecule involved in tissue destruction and fibrosis. The inhibition of IL-1 action has clinical efficacy in many inflammatory diseases, such as hereditary autoinflammatory disorders, familial hereditary fever, gout, rheumatoid arthritis and type 2 diabetes mellitus (T2DM). The latter is a common metabolic condition caused by insulin resistance and pancreatic beta-cell failure, the causes of both of which have inflammatory components. IL-1 signaling has roles in beta-cell dysfunction and destruction via the NFkappaB and mitogen-activated-protein-kinase pathways, leading to endoplasmic reticulum and mitochondrial stress and eventually activating the apoptotic machinery. In addition, IL-1 acts on T-lymphocyte regulation. The modulating effect of IL-1 on the interaction between the innate and adaptive immune systems and the effects of IL-1 on the beta-cell point to this molecule being a potential interventional target in autoimmune diabetes mellitus. Genetic or pharmacological abrogation of IL-1 action reduces disease incidence in animal models of type 1 diabetes mellitus (T1DM) and clinical trials have been started to study the feasibility, safety and efficacy of IL-1 therapy in patients with T1DM. Here, we review the rationale for blocking IL-1 in patients with T1DM.

MeSH Terms
Animals Clinical Trials as Topic Diabetes Mellitus, Type 1/drug therapy,metabolism,therapy Humans Hypoglycemic Agents/therapeutic use Interleukin-1/antagonists & inhibitors,genetics,metabolism
Chemicals
Hypoglycemic Agents Interleukin-1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mandrup-Poulsen Thomas
Hagedorn Research Institute, 6 Niels Steensensvej, DK-2820 Gentofte, Denmark. [email protected]
Pickersgill Linda
Donath Marc Yves
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Article Info
Journal
Nature reviews. Endocrinology
Abbr.
Nat Rev Endocrinol
ISSN
1759-5037
DOI
10.1038/nrendo.2009.271
Email
[email protected]
Published
2010-03-00
Pages
158-66
Language
English
Region
England
NLM ID
101500078
Subset
IM
External Links
PubMed source DOI: 10.1038/nrendo.2009.271 View journal details
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