Interleukin 1 family

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 21.01.2024

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Acute phase protein inducing factor (APPIF); B cell activating factor (BAF oder BCAF = Il-1α); B cell differentiation factor (BCDF oder BDF); Corneal epithelial cell derived thymocyte activating factor (CETAF); Epidermal cell derived thymocyte activating factor (ETAF); Fibroblast activating factor (FAF); Haematopoietin-1 (H-1; haematopoietin-1 (H-1 Il-1β); Haptoglobin inducing activity; IL-1; Il-1β); LAF; Leucocyte endogenous mediator (LEM = Il-1α); leukocytic pyrogenic (LP); Lymphocyte activating factor; Macrophage derived T cell replacing factor (TRFM); mitogenic protein (MP = Il-1α); Mononuclear cell factor (MCF); muscle proteolysis-inducing factor (MPIF); Osteoclast activating factor (OAF = Il-1β); Serum amyloid A inducer (SAA inducer); Shymocyte mitogenic protein (TMP); Thymocyte activating factor (TAF); Thymocyte proliferation factor (TPF); Thymocyte stimulating factor (TSF); Tumor inhibitory factor-2 (= Il-1α)

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Interleukin-1 was first described as an "endogenous pyrogen" in the middle of the last century.

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The interleukin (IL)-1 cytokine family comprises 11 members, including:


IL-1beta and IL-18 are produced as biologically inert propeptides; their activation requires proteolytic cleavage by caspase-1. N-terminal processing is also required for the full activity of IL-36 cytokines (Palomo J et al.2015).

The IL-1 receptor (IL-1R) family comprises 10 members with cytokine-specific receptors, co-receptors and inhibitory receptors. The signaling IL-1Rs have a common structure with three extracellular immunoglobulin (Ig) domains and one intracellular Toll-like/IL-1R (TIR) domain.

Interleukin-1 can be formed by numerous inducers and pathological processes, such as antigen-antibody complexes, lipopolysaccharides, phytohemagglutinins (lectins), muramyl dipeptides, various cytokines such as interleukin-2 or TNFs (tumor necrosis factors); furthermore non-specifically by histamine, bacterial endotoxins and by general inflammatory processes.

Interleukin-1 cytokines bind to their specific receptors, which leads to the recruitment of a co-receptor and intracellular signal transmission. Interleukin-1 cytokines trigger strong inflammatory reactions. Their activity is tightly controlled by naturally occurring inhibitors. Some of these inhibitors are antagonists of the IL-1 family, while others are members of the IL-1R family (interleukin-1 receptor family) and act as membrane-bound or soluble decoy receptors.

An imbalance between agonist and antagonist levels can lead to exaggerated inflammatory reactions. The production of interleukin-1 is inhibited via an endogenous feedback mechanism. Interleukin-6 and prostaglandin E2 also have an inhibitory effect.

General information
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The effects of interleukin-1 on different cell systems:

  • Blood and endothelial cells: By influencing blood and endothelial cells, interleukin-1 plays a central role in the processing of immunological processes (e.g. in inflammation and wound healing processes). Here, interleukin-1 acts synergistically with other cytokines. On endothelial cells, interleukin-1 induces the expression of cell adhesion molecules (e.g. ICAM; adhesion molecules) and various chemokines. chemokines.
  • T lymphocytes: Interleukin-1 activates T lymphocytes, especially T helper cells. Interleukin-1-activated cells secrete interleukin-2.
  • B lymphocytes: Interleukin-1 enhances the proliferation and maturation of B lymphocytes and thereby initiates or accelerates B cell-mediated immune responses.
  • Macrophages: Interleukin-1 induces the synthesis of prostaglandin E2 and TNFalpha in macrophages.
  • Neutrophil leukocytes: Interleukin-1 promotes migration and stimulation of metabolic processes.
  • Hepatocytes: Interleukin-1 induces the production of acute phase proteins (e.g. C-reactive protein and fibrinogen).
  • CNS: Interleukin-1 has important functions in the brain. The cytokine can be detected in increased amounts in the hypothalamus and is jointly responsible for the stimulation of corticotropin-releasing hormone in inflammatory processes. In astrocytes, interleukin-1 induces the formation of interleukin-6, TNFalpha and GMCSF. Together with these cytokines, it is involved in fever reactions (endogenous pyrogen).
  • Osteoclasts/polyarthritis: Interleukin-1 activates osteoclasts. The cytokine plays an important role in the pathogenesis of polyarthritis and rheumatoid arthritis. Patients with rheumatoid arthritis have an increased production of interleukin-1. The cytokine is mainly found in inflamed joints, where it is deposited in chondrocytes. In an inflamed joint, the interleukin-1-triggered activation of osteoclasts leads to an uncontrolled, focal breakdown of the bone. Inflammatory pannus penetrates into the resulting bone gaps and prevents the physiologically occurring repair.
  • Chondrocytes: Interleukin-1 attaches itself to chondrocytes. It induces the release of cartilage-destroying enzymes and thus leads to the breakdown of cartilage substance and the destruction of the joint. Intra-articularly injected interleukin-1 antagonists are seen as a potential treatment option for early forms of osteoarthritis.
  • Keratinocytes: Interleukin-1alpha (originally known as "ETAF") plays an important role in maintaining skin barrier function and in various immune responses. Due to its ability to stimulate collagen synthesis, it is used in the cosmetics industry.

General therapy
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The activity of an interleukin-1-mediated inflammatory process can be reduced or completely suppressed with antibodies against interleukin-1beta itself(canakinumab) and against the interleukin-1 receptor(anakinra).

Canakinumab binds IL-1beta circulating in the blood and improves the symptoms of cryopyrin-associated periodic syndrome (CAPS).

Anakinra improves the symptoms of rheumatoid arthritis, adult Still's syndrome and idiopathic cold urticaria.

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Interleukin-1 is an extremely versatile mediator substance of the immune system. Interactions with target cells take place via receptors and cause numerous, different, organ-related functions. Due to the diverse functions, numerous synonyms, mostly related to one cell system, result for this now well defined cytokine, e.g. "Epidermal cell derived thymocyte activating factor", also called ETAF or "Fibroblast activating factor", also called FAF, etc.

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Last updated on: 21.01.2024