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Interleukin 1 beta (IL-1β)

Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis.

Interleukin 1 beta (IL-1β) is a cytokine protein that in humans is encoded by the IL1B gene.

There are two genes for interleukin-1 (IL-1): IL-1 alpha and IL-1 beta.

IL-1β precursor is cerated by cytosolic caspase 1 (interleukin 1 beta convertase) to form mature IL-1β.

Gene location Chromosome 2 

The interleukin 1 family consists of both pro and anti inflammatory mediators and there are 9 genes that encode different forms of interleukin 1, like Il-1a and IL-1B.

IL-1B is one of the most prominent mediators of inflammation and its secretion is tightly regulated given its potent nature.

IL-1β is a member of the interleukin 1 family of cytokines. 

This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). 

It is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. 

IL-1B starts in an inactive form and is induced first by toll like receptors or TNFa and requires a second stimulus by thE inflammasome to induce the mature, active form of IL-1B.

The induction of cyclooxygenase-2 (PTGS2/COX2) by IL-1B cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. 

This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.

IL-1β, in combination with IL-23, induces expression of IL-17, IL-21 and IL-22 by γδT cells, suggesting IL-1β is involved in modulation of autoimmune inflammation.

Inflammasomes recognize danger signals and activate proinflamatory process and production of IL-1β and IL-18. 

NLRP3  which contains three domains: pyrin domain, a nucleotide-binding domain and a leucine-rich-repeat type of inflammasome.

NLRP3 is activated by various stimuli.

 There  are documented several diseases connected to NLRP3 activation like type 2 diabetes mellitus , Alzheimer’s disease, obesity and atherosclerosis.

The molecular weight of the proteolytically processed IL-1β is 17.5 kDa. 

Increased production of IL-1β causes a number of different autoinflammatory syndromes: the monogenic conditions referred to as Cryopyrin-Associated Periodic Syndromes (CAPS), due to mutations in the inflammasome receptor NLRP3 which triggers processing of IL-1B.

Intestinal dysbiosis induced osteomyelitis through a IL-1β dependent manner.

The presence of IL-1β has been also found in patients with multiple sclerosis.

It is not known exactly which cells produce IL-1β. 

Treatment of multiple sclerosis with glatiramer acetate or natalizumab has also been shown to reduce the presence of IL-1β or its receptor.

Several types of inflammasomes are suggested to play role in tumorgenesis due to their immunomodulatory properties, modulation of gut microbiota, differentiation and apoptosis. 

Over-expression of IL-1β caused by NLRP3 inflammasome polymorphisms may result in carcinogenesis: colon cancer and melanoma. 

The IL-1 family plays important role in inflammation in many degenerative diseases, such as age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa. 

The inflammatory process including NLRP3 upregulation is one of the causes of age-related macular degeneration and other retinal diseases that lead to vision loss.

Anakinra is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. 

Anakinra blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin type 1 receptor, which is expressed in a wide variety of tissues and organs. 

Canakinumab is a human monoclonal antibody targeted at IL-1B, and used  for treatment of cryopyrin-associated periodic syndromes.

 

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