PMID- 20173777
OWN - NLM
STAT- MEDLINE
DCOM- 20100521
LR  - 20211020
IS  - 1759-5037 (Electronic)
IS  - 1759-5029 (Linking)
VI  - 6
IP  - 3
DP  - 2010 Mar
TI  - Blockade of interleukin 1 in type 1 diabetes mellitus.
PG  - 158-66
LID - 10.1038/nrendo.2009.271 [doi]
AB  - 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.
FAU - Mandrup-Poulsen, Thomas
AU  - Mandrup-Poulsen T
AD  - Hagedorn Research Institute, 6 Niels Steensensvej, DK-2820 Gentofte, Denmark. 
      tmpo@hagedorn.dk
FAU - Pickersgill, Linda
AU  - Pickersgill L
FAU - Donath, Marc Yves
AU  - Donath MY
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Nat Rev Endocrinol
JT  - Nature reviews. Endocrinology
JID - 101500078
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Interleukin-1)
SB  - IM
MH  - Animals
MH  - Clinical Trials as Topic
MH  - Diabetes Mellitus, Type 1/drug therapy/*metabolism/therapy
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Interleukin-1/antagonists & inhibitors/genetics/*metabolism
RF  - 88
EDAT- 2010/02/23 06:00
MHDA- 2010/05/22 06:00
CRDT- 2010/02/23 06:00
PHST- 2010/02/23 06:00 [entrez]
PHST- 2010/02/23 06:00 [pubmed]
PHST- 2010/05/22 06:00 [medline]
AID - nrendo.2009.271 [pii]
AID - 10.1038/nrendo.2009.271 [doi]
PST - ppublish
SO  - Nat Rev Endocrinol. 2010 Mar;6(3):158-66. doi: 10.1038/nrendo.2009.271.