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 Β-cell failure, the causes of both of which have inflammatory components. IL-1 signaling has roles in Β-cell dysfunction and destruction via the NFB 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 Β-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.
| Original language | English |
|---|---|
| Journal | Nature Reviews Endocrinology |
| Volume | 6 |
| Pages (from-to) | 158-166 |
| Number of pages | 9 |
| Publication status | Published - Mar 2010 |
