Interleukin 1beta also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokineprotein that in humans is encoded by the IL1Bgene. There are two genes for interleukin-1 : IL-1 alpha and IL-1 beta. IL-1β precursor is cleaved by cytosolic caspase 1 to form mature IL-1β.
Function
The fever-producing property of human leukocytic pyrogen was purified by Dinarello in 1977 with a specific activity of 10–20 nanograms/kg. In 1979, Dinarello reported that purified human leukocytic pyrogen was the same molecule that was described by Igal Gery in 1972. He named it lymphocyte-activating factor because it was a lymphocyte mitogen. It was not until 1984 that interleukin 1 was discovered to consist of two distinct proteins, now called interleukin-1 alpha and interleukin-1 beta. 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. This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 by this cytokine in the central nervous system 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, induced expression of IL-17, IL-21 and IL-22 by γδT cells. This induction of expression is in the absence of additional signals. That suggests IL-1β is involved in modulation of autoimmune inflammation Different inflammasome complex - cytosolic molecular complex - have been described. Inflammasome recognize danger signals and activate proinflamatory process and production of IL-1β and IL-18. NLRP3 type of inflammasome is activated by various stimuli and there are documented several diseases connected to NLRP3 activation like type 2 diabetes mellitus, Alzheimer's disease, obesity and atherosclerosis.
Properties
The molecular weight of the proteolytically processed IL-1β is 17.5 kDa. IL-1β has the following amino acid sequence:
Several types of inflammasomes are suggested to play role in tumorgenesis due to their immunomodulatory properties, modulation of gut microbiota, differentiation and apoptosis. Over-expresion of IL-1β caused by inflammasome may result in carcinogenesis. Some data suggest that NLRP3 inflammasome polymorphisms is connected to malignancies such as colon cancer and melanoma. It was reported that IL-1β secretion was elevated in the lung adenocarcinomacell line A549. Another study showed that inhibition of inflammasome and IL-1β expresion decreased development of cancer cells in melanoma.
Retinal degeneration
It has been shown that IL-1 family plays important role in inflammation in many degenerative diseases, such as age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa. Significantly increased protein level of IL-1β has been found in the vitreous of diabetic retinopathy patient. The role of IL-1β has been investigated for potential terapeutic target for treatment of diabetic retinopathy. However, systemic using of canakinumab did not have an significant effect. The role of IL-1β in age-related macular degeneration has not been proven in patient, but in many animal models and in vitro studies it has been demonstrated the role of IL-1β in retinal pigmented epithelial cells and photoreceptor cells damage. NLRP3 inflammasome activate caspase-1 which catalyze cleavage of inactive cytosolic precursor pro-IL-1β to its mature form IL-1β. Retinal pigmented epithelial cells forms blood retinal barrier in human retina which is important for retinal metabolic activity, integrity and inhibition of immune cells infiltration. It has been shown that human retinal pigmented epithelial cells can secrete IL-1 β in exposure to oxidative stress. The inflammatory reaction leads to damage of retinal cells and infiltration of cells of the immune system. 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.
Because many authors of scientific manuscripts make the minor error of using a homoglyph, sharp s, instead of beta, mentions of "IL-1ß" often become "IL-1ss" upon automated transcoding. This is why so many mentions of the latter appear in web search results.
