Interleukin 1 beta

Mammalian protein found in Homo sapiens

Interleukin 1 beta (IL 1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, 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 (this gene). IL 1β precursor is cleaved by cytosolic caspase 1 (interleukin 1 beta convertase) to form mature IL 1β.

The fever producing property of human leukocytic pyrogen (interleukin 1) 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 (LAF) 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, in combination with IL 23, induced expression of IL 17, IL 21 and IL 22 by γδ T 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. Inflammasomes recognize danger signals and activate proinflammatory process and production of IL 1β and IL 18. NLRP3 (contains three domain: pyrin domain, a nucleotide binding domain and a leucine rich repeat) 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.

Before cleavage by caspase 1, pro IL 1β has a molecular weight of 37 kDa.

Increased production of IL 1β causes a number of different autoinflammatory syndromes, most notably the monogenic conditions referred to as Cryopyrin Associated Periodic Syndromes (CAPS), due to mutations in the inflammasome receptor NLRP3 which triggers processing of IL 1β. Intestinal dysbiosis has been observed to induce osteomyelitis through a IL 1β dependent manner. The presence of IL 1β has been also found in patients with multiple sclerosis (a chronic autoimmune disease of the central nervous system). However, 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 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 adenocarcinoma cell line A549. It has also been shown in another study that IL 1β, together with IL 8, plays an important role in chemoresistance of malignant pleural mesothelioma by inducing expression of transmembrane transporters. Another study showed that inhibition of inflammasome and IL 1β expression decreased development of cancer cells in melanoma. Furthermore, it has been found that in breast cancer cells, IL 1β activates p38 and p42/22 MAPK pathways which ultimately lead to the secretion of the RANK/RANKL inhibitor osteoprotegerin. Higher osteoprotegerin and IL 1β levels are a characteristic of breast cancer cells with a higher metastatic potential.

The human immunodeficiency virus (HIV) infects cells of the immune system, such as macrophages, dendritic cells, and CD4+ T helper cells (TH). The latter can be infected by the virus in various ways with different fates depending on the state of activation of the T helper cell. Firstly, TH cells can die of viral lysis due to an active infection that produces enough virions to kill the cell. Secondly, CD4+ T cells can be infected by the virus but instead of producing more viral particles, the cell enters a latent phase. In this period, the T helper cells looks identical from the outside but any stressor could lead to the renewed production of HIV and its propagation to new immune cells. Lastly, the TH cell can become abortively infected, where the virus gets detected inside the cell and a programmed cell death, known as pyroptosis, kills the infected cell. Pyroptosis is mediated via caspase 1 and is characterized by cell lysis and the secretion of IL 1β causing inflammation and attraction of more immune cells. This can create a cycle of CD4+ T cells getting abortively infect with HIV, dying of pyroptosis, new T helper cells arriving to the site of inflammation where they get infected again. The results is the depletion of T helper cells. Even though, levels of IL 1β in blood are not majorly different between HIV positive and negative individuals, studies have shown elevated levels of IL 1β of lymphatic tissue in HIV infected individuals. Additionally, it has been shown that caspase 1 is upregulated in the retina of diabetic patients, causing a higher production of IL 1β and subsequent death of retinal neurons.

Studies in mice on experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS) research, have found that blocking IL 1β could make the animals resistant to EAE. IL 1β led to the production of an antigen specific pro inflammatory subset of T helper cells (TH17). In combination with other cytokines, interleukin 1β can upregulate the production of the cytokine GM CSF which is correlated to neuroinflammation. Detailed mechanisms on this front are yet to be elucidated. IL 1β has also been observed in elevated levels of the cerebrospinal fluid and brain tissues of Alzheimer patients. The amyloid β plaques, that are characteristic of Alzheimer disease, are damage associated molecular patterns (DAMPs) that are recognized by pattern recognition receptors (PRRs) and lead to the activation of microglia. Consequently, microglia release interleukin 1β among other cytokines. Nevertheless, the significance of IL 1β in Alzheimer disease and the onset of neuroinflammation still remains largely unknown.

Because many authors of scientific manuscripts make the minor error of using a homoglyph, sharp s (ß), instead of beta (β), mentions of "IL 1ß" [sic] often become "IL 1ss" [sic] upon automated transcoding (because ß transcodes to ss). This is why so many mentions of the latter appear in web search results.