IL-1 (interleukin 1) is the first member of the IL-1 family which is closely linked to the innate immune response. IL-1 affects virtually all cells and organs and is a major pathogenic mediator of autoinflammatory, autoimmune, infectious, and degenerative diseases.
Herein, we will mainly discuss IL-1 (interleukin 1) discovery & structure, IL-1 (interleukin 1) receptor, and IL-1 (interleukin 1) function.
IL-1 (interleukin 1) was first described as a protein inducing fever and was called human leukocytic pyrogen. After cloning of IL-1β cDNA, it was demonstrated that recombinant IL-1β produced fever in human beings. In the same year, 2 cDNAs for IL-1 were reported, and its cloning resulted in the expression of 2 related proteins, termed IL-1α and IL-1β. Now, 11 members of the IL-1 family exist.
Genes for IL-1α, IL-1β, and IL-1Ra are closely associated in the region of 2q12-q21 of human chromosome 2. Human IL-1α and IL-1β share low sequence homology and are synthesized as 31 kd, variably glycosylated pro-cytokines that share 25% amino acid identity across their entire precursor structure and 22% amino acid identity over their mature segments. The mature forms of these 2 cytokines have a single β-trefoil domain that is shared with fibroblast growth factors.
IL-1 (interleukin 1) receptor belongs to the Toll-IL-1-receptor (TIR) superfamily, which is defined by an intracellular TIR domain that initiates the signaling cascade. TIR receptors can be divided into 2 subgroups regarding the extracellular domains. One group contains a leucine-rich repeat motif, and the other group is characterized by an immunoglobulin-like domain. TLRs belong to the group with the leucine-rich repeat motif, whereas the immunoglobulin domain subgroup includes the IL-1Rs. IL-1α and IL-1β exert their similar effects by binding to IL-1RI. They can also bind to IL-1RII, which is in contrast, acting as a decoy receptor and not involved in signal transduction.
IL-1α and IL-1β, produced by activated macrophages and monocytes, are one of the key players in the innate immune response. They play an important role in coordination of local and systemic inflammation by causing inflammation and inducing the expression of other proinflammatory genes like COX type II, inducible nitric oxide synthase, and other cytokines or chemokines.
IL-1β is the most powerful endogenous pyrogen known and has been implicated in tissue damage and systemic symptoms of sepsis and several inflammatory diseases. Therefore IL-1 (interleukin 1) has been an early target in the therapy of a number of diseases.
Rilonacept, an anti IL-1 targeted therapy, is used for familial chylomicronemia syndrome (FCS), cryopyrin-associated periodic syndromes (CAPS) and muckle-wells syndrome (MWS).
Canakinumab, an anti IL1B tageted therapy, is used for systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome and familial mediterranean fever.
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