Interleukins

Anthony Meager, The National Institute for Biological Standards and Control, South Mimms, Herts, UK
Meenu Wadhwa, The National Institute for Biological Standards and Control, South Mimms, Herts, UK

Published online: July 2007

DOI: 10.1002/9780470015902.a0000932.pub2

The interleukins (IL) belong to a category of biologically active proteins, termed cytokines. These proteins are derived mainly from white blood cells and act on white cells, although these criteria are not necessarily exclusive of other cell sources and activities. Interleukins, among other proteins, maintain the haematopoietic and immune systems and control their functions. They have been classified specifically by a designated nomenclature committee of the International Union of Immunological Societies/World Health Organization. In general, numbering of interleukins has followed the order of their discovery and this has led to some anomalies. It has become evident that interleukins can be classified into subgroups or families based on shared structural characteristics, and/ or shared receptor subunits and/or shared chromosomal locations. For example, IL-1, IL-1, IL-18 and IL-33 belong to the ‘IL-1 family’, IL-2, IL-15 and IL-21 to the ‘IL-2 family’ (IL-4, IL-7, IL-9 and IL-13 might also be included as they share at least one receptor subunit with IL-2 family members), IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29 to the ‘IL-10 family’, IL-12, IL-23 and IL-27 to the ‘IL-12 family’. IL-3 and IL-5 together with GM-CSF and IL-6 and IL-11 together with several other noninterleukin named cytokines – LIF, OSM, CNTF, CT-1 – can also be grouped as families of ‘like’ cytokines. The IL-17 family is comprised of six related proteins (IL-17A–F), one of which, the murine homologue of IL-17E, was anomalously designated IL-25. With hindsight, the remaining interleukins might have been better classified with other biological modifiers. For instance, IL-8 is clearly a chemokine; IL-14 and IL-16 bear scant resemblance to any other interleukins, or other cytokines for that matter.

In the following paper, the molecular characteristics of interleukin proteins, their cognate receptors and intracellular signalling pathways and their biological activities are briefly described. The interactions of particular interleukins in the regulation of immune cell growth, differentiation and function will be illustrated by short sections at the end of the paper covering (1) T-lymphocyte development and activation and (2) chronic inflammation and autoimmunity.

Keywords: interleukins; cytokines; receptors; bioactivities

Figure 1. Schematic diagram of the proposed interleukin-regulated pathways for the differentiation and development of functional T-cell subsets. Each T helper (TH) subset expresses a unique ‘portfolio’ of interleukins and other cytokines that pertains to their function: TH1 subset upregulates cell-mediated immunity; TH2 subset provides ‘help’ for humoral immune responses, including immunoglobulin production from B cells and mast cells; TH17 subset probably provides ‘early’ defence against large injuries and infections. CD8+ T cells form the majority of cytotoxic T lymphocytes (CTL), which attack and kill foreign antigen-presenting cells. Once the injury/ infection is resolved, the functional responsiveness of T cells is shutdown by IL-10 and TGF1 secreted by Regulatory T cells (TReg) (see Figure 2). Memory T cells then may develop, which are sustained by IL-7.
Figure 2. Schematic diagram illustrating the proposed interactions of pro- (black) and anti- (red) inflammatory interleukins and other cytokines in the mediation of acute and chronic inflammation. The chemokine IL-8 released from TH17 cells forms a chemotactic gradient to attract neutrophils (N) to sites of injury and infection. The expression of cellular adhesion molecules, e.g. intercellular adhesion molecule-1 (ICAM-1), is markedly increased by IL-1, IL-17A and TNF leading to neutrophil adherence to the endothelial cells lining blood capillaries, following which N transmigrate into the injured/infected tissue. Neutrophils and T-cell infiltrates (not shown) release more pro-inflammatory interleukins and cytokines to resolve the injury/infection, but which may lead, if not appropriately regulated, to aggressive T cell-mediated attack on host tissues and ultimately to profound autoimmune disease.
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Cytokines | Proteins: Structure, Function, Metabolism
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Article Title: Interleukins
 
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Meager, Anthony, and Wadhwa, Meenu(Jul 2007) Interleukins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000932.pub2]