Interleukins are a group of cytokines that were first seen to be expressed by leukocytes. The term interleukin describes a variety of polypeptides that act specifically as mediators between leucocytes. However, the name interleukin is something of a relic, since it has been found that interleukins are produced by a wide variety of body cells.
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Interleukins are a group of cytokines that were first seen to be expressed by leukocytes. The term interleukin describes a variety of polypeptides that act specifically as mediators between leucocytes. However, the name interleukin is something of a relic, since it has been found that interleukins are produced by a wide variety of body cells. The majority of interleukins are synthesized by helper CD4+ T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. The function of the immune system depends in a large part on interleukins. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Rare deficiencies of a number of Interleukins have been described, all featuring autoimmune diseases or immune deficiency.
The majority of interleukin cytokines can be divided into specific families based on structure and function. The 3-dimensional structure of the mature forms of each member of the human interleukin-1 superfamily is composed of 12-14 β-strands producing a barrel-shaped protein. The cytokines of interleukin-1 superfamily are key molecules both in the innate and in the adaptive immune response. Inclusion in the interleukin-6 family is based on a helical cytokine structure, shared receptor subunit makeup and activation of the signal transducing receptor protein glycoprotein 130 (gp130). Interleukin-10 is the prototypic member of the interleukin-10 cytokine family, which also include IL-19, IL-20, IL-22, IL-24 and IL-26.The interleukin-12 family cytokines, including IL-12, IL-23, IL-27 and IL-35, are key players in the regulation of T cell responses. All members of the interleukin-17 family have a similar protein structure, with four highly conserved cysteine residues critical to their 3-dimensional shape. There are still other interleukin molecules, which are currently not included in a defined family, such as, IL-13, IL-16, IL-32, IL-34, etc.
The Interleukin-1 superfamily & Interleukin-1 receptor family plays critical roles in initiating and promoting the host response to injury or infection, including fever, sleep, acute phase protein synthesis, chemokine production, adhesion molecule up-regulation and production and release of matrix metalloproteinases and growth factors. The original members of the Interleukin-1 superfamily are IL-1α, IL-1β, and the IL-1 receptor antagonist (IL-1RA). Six additional members of this family have since been described: IL-1F5, IL-1F6, IL-1F7, IL-1F8, IL-1F9, IL-1F10, with structural homology to IL-1α, IL-1β or IL-1RA. Another molecule described as a member of Interleukin-1 superfamily is IL-18. Recently, a further putative member of the Interleukin-1 superfamily has been described that is called IL-33.
Interleukin-6 family of cytokines includes IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-like cytokine (CLC) and cardiotrophin-1 (CT-1). Members of the interleukin-6 family cytokines utilize one or both of the shared receptor signal transducing subunits, gp130 and LIF receptor (LIFR). Interleukin-6 family cytokines binding of gp130 activates the JAK/STAT signaling pathway, which functions in many biological processes. Interleukin-6 and their receptor have been implicated in prostate cancer progression.
Interleukin-10, also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. IL-10 shares use of IL-10 receptor 2 (IL-10R2) in cell signaling with other members of this family (L-22, IL-26) and interferon-like molecules (limitin, L-28A, IL-28B, IL-29). The interleukin-10 family, interferons and interferon-like molecules constitute the Class 2 alpha-helical cytokines, which initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms.
The interleukin-12 family cytokines are key players in the regulation of T cell responses. Interleukin-12 has long been appreciated to play central role in the generation of TH1 cells. Subsequent studies indicated that two closely related interleukins, IL-23 and IL-27, also regulate TH1-cell responses. IL-35, a novel member of interleukin-12 family, is secreted by regulatory T cells, and suppresses inflammatory responses of immune cells. Function of the interleukin-12 family members largely depend on interleukin -12 family receptors.
Cytokines of the interleukin-17 family include IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (or IL-25), and IL-17F. Interleukin-17 family members have been reported to function in numerous immune processes. Most notably, IL-17 is involved in inducing and mediating proinflammatory responses. This proinflammatory activity is exemplified by their involvement in pulmonary inflammatory responses. Both IL-17A and IL-17F are involved in the recruitment of neutrophils, and IL-17E is able to induce Th2 cytokine production and eosinophilia. Cytokines of interleukin-17 family are all well conserved in mammals, with as much as 62–88% of amino acids conserved between the human and mouse homologs.