Interleukin-1

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 07.08.2022

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Synonym(s)

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)

Definition
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Interleukin-1 was first described in the middle of the last century as an "endogenous pyrogen". It is mainly produced by activated monocytes and macrophages, but also by other cells such as keratinocytes, endothelial cells, astrocytes, NK cells, neutrophil granulocytes, B lymphocytes, T lymphocytes, dendritic cells and various tumor cells (e.g. melanoma cells). Tumor cells (e.g. melanoma cells).

Interleukin-1 exists in two different forms with largely similar functions:

  • Interleukin-1alpha

and

  • interleukin-1beta.

Both interleukin-1 fractions are encoded by different genes located on chromosome 2(IL1A gene/IL1B gene).

Interleukin-1 can be produced by numerous inducers and processes, such as antigen-antibody complexes, lipopolysaccharides, phytohemagglutinins (lectins), muramyl dipeptides, various cytokines such as interleukin-2 or TNF (tumor necrosis factor); furthermore, unspecifically by histamine, bacterial endotoxins and by general inflammatory processes.

The production of interleukin-1 is inhibited by an endogenous feedback mechanism. Interleukin-6 and prostaglandin E2 also have an inhibitory effect.

The biological action of interleukin-1 is initiated via its interleukin-I receptors. The signal transduction pathway triggered by the activated receptor is via adenylate cyclase. Activation of this enzyme leads to an increase in intracellular cAMP levels. In addition, the transcription factor NF-kappaB is activated.

Interleukin-1 receptors are distinguished into 2 different affinity forms:

  • Type 1 (identical to CD121a) is a high-affinity, membrane-bound receptor in T lymphocytes and other cells.
  • Type 2 (identical to CD121b) is expressed on B lymphocytes and myelomonocytic cells.

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 inflammatory and wound healing processes). Here, interleukin-1 acts synergistically with other cytokines. At endothelial cells, interleukin-1 induces the expression of cell adhesion molecules (e.g. ICAM; adhesion molecules) and various other cytokines. chemokines.

T lymphocytes: Interleukin-1 activates T lymphocytes, especially T helper cells. When activated by interleukin-1, these cells serinate interleukin-2.

B-Lymphocytes: Interleukin-1 enhances the proliferation and maturation of B-lymphocytes and thereby initiates or accelerates B-cell mediated immune reactions.

Macrophages: Interleukin-1 induces the synthesis of prostaglandin E2 and TNFalpha in macrophages.

Neutrophil leukocytes: Interleukin-1 promotes the 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 takes on important functions in the brain. The cytokine can be detected in the hypothalamus and is jointly responsible for the stimulation of the corticotropin-releasing hormone in inflammatory processes. In astrocytes, interleukin-1 induces the formation of interleukin-6, TNFalpha and GMCSF. It is involved with these cytokines 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 show an increased production of interleukin-1. The cytokine is mainly found in the inflamed joints, where it is deposited in chondrocytes. In an inflamed joint, the interleukin-1-triggered activation of osteoclasts leads to an uncontrolled, focal bone breakdown. Inflammatory pannus penetrates the resulting bone gaps and thus prevents physiological 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. Intraarticularly injected interleukin-1 antagonists are considered a potential therapeutic option for early forms of osteoarthritis.

Epidermis: Interleukin-1alpha (originally known as "ETAF") plays an important role in maintaining the skin barrier function as well as in various immune reactions. It is used in the cosmetic industry due to its ability to stimulate collagen synthesis.

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 symptoms in rheumatoid arthritis, adult breastfeeding syndrome and idiopathic cold urticaria.

Note(s)
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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.

Literature
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  1. Afonina IS et al (2015) Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme. Immunity 42:991-1004.
  2. Cavalli G et al (2015) Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford) 54:2134-2144.
  3. Brough D et al (2015) Interleukin-1 as a pharmacological target in acute brain injury. Exp Physiol 100:1488-1494.
  4. Kahlenberg JM (2016) Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade. Curr Opin Rheumatol 28:197-203.
  5. Ridker PM (2016) From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection. Circ Res 118:145-156.
  6. Schett G et al (2016) Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol 12:14-24.
  7. Vitale A et al. (2016) .interleukin-1 inhibition in Behçet's disease. Isr Med Assoc J 18(3-4):171-176.
  8. Wechalekar MD et al (2014) The efficacy and safety of treatments for acute gout: results from a series of systematic literature reviews including Cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors. J Rheumatol Suppl 92:1525.

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Last updated on: 07.08.2022