Interleukin

Interleukins (ILs) are a group of

The term interleukin derives from (inter-) "as a means of communication", and (-leukin) "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes". The name is something of a relic; it has since been found that interleukins are produced by a wide variety of body cells. The term was coined by Dr Vern Paetkau, University of Victoria.

Some interleukins are classified as lymphokines, lymphocyte-produced cytokines that mediate immune responses.

Common families

Interleukin 1

Interleukin 1 alpha and interleukin 1 beta (

The crystal structures of IL1A and IL1B[9] have been solved, showing them to share the same 12-stranded beta-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors.^[10] The beta-sheets are arranged in 4 similar lobes around a central axis, 8 strands forming an anti-parallel beta-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

Molecular cloning of the Interleukin 1 Beta converting enzyme is generated by the proteolytic cleavage of an inactive precursor molecule. A complementary DNA encoding protease that carries out this cleavage has been cloned. Recombinant expression enables cells to process precursor Interleukin 1 Beta to the mature form of the enzyme.

Interleukin 1 also plays a role in the

T lymphocytes regulate the growth and differentiation of T cells and certain B cells through the release of secreted protein factors.^[12] These factors, which include interleukin 2 (IL2), are secreted by lectin- or antigen-stimulated T cells, and have various physiological effects. IL2 is a lymphokine that induces the proliferation of responsive T cells. In addition, it acts on some B cells, via receptor-specific binding,^[13] as a growth factor and antibody production stimulant.^[14] The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity.^[13] Solution NMR suggests that the structure of IL2 comprises a bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly defined loops. Residues in helix A, and in the loop region between helices A and B, are important for receptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF).^[14]

Interleukin 3

IL3 is produced by T lymphocytes and T-cell lymphomas only after stimulation with antigens, mitogens, or chemical activators such as phorbol esters. However, IL3 is constitutively expressed in the myelomonocytic leukaemia cell line WEHI-3B.[16] It is thought that the genetic change of the cell line to constitutive production of IL3 is the key event in development of this leukaemia.^[16]

Interleukin 4

Interleukin 4 (IL4) is produced by CD4⁺ T cells specialized in providing help to B cells to proliferate and to undergo class switch recombination and somatic hypermutation. Th2 cells, through production of IL-4, have an important function in B-cell responses that involve class switch recombination to the IgG1 and IgE isotypes.

Interleukin 5

Interleukin 5 (IL5), also known as eosinophil differentiation factor (EDF), is a lineage-specific cytokine for eosinophilpoiesis.^[17][18] It regulates eosinophil growth and activation,^[17] and thus plays an important role in diseases associated with increased levels of eosinophils, including asthma.^[18] IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF),^[18] but while these exist as monomeric structures, IL5 is a homodimer. The fold contains an anti-parallel 4-alpha-helix bundle with a left handed twist, connected by a 2-stranded anti-parallel beta-sheet.^[18][19] The monomers are held together by 2 interchain disulphide bonds.^[19]

Interleukin 6

Interleukin 6 (IL6), also referred to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of biological functions.^[20] It plays an essential role in the final differentiation of B cells into immunoglobulin-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation, and, in hepatocytes, acute-phase reactants.^[20][21]

A number of other cytokines may be grouped with IL6 on the basis of sequence similarity.^[20][21][22] These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting the production, differentiation, and function of two related white cell groups in the blood.^[22] MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.

Cytokines of the IL6/GCSF/MGF family are glycoproteins of about 170 to 180 amino acid residues that contain four conserved cysteine residues involved in two disulphide bonds.^[22] They have a compact, globular fold (similar to other interleukins), stabilised by the two disulphide bonds. One half of the structure is dominated by a 4-alpha-helix bundle with a left-handed twist;^[23] the helices are anti-parallel, with two overhand connections, which fall into a double-stranded anti-parallel beta-sheet. The fourth alpha-helix is important to the biological activity of the molecule.^[21]

Interleukin 7

Interleukin 7 (IL-7)^[24] is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages.

Interleukin 8

Interleukin 8 is a

There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response.

Interleukin 9

Interleukin 9 (IL-9)^[30] is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T cells. Early studies had indicated that Interleukin 9 and 7 seem to be evolutionary related ^[31] and Pfam, InterPro and PROSITE entries exist for interleukin 7/interleukin 9 family. However, a recent study ^[32] has shown that IL-9 is, in fact, much closer to both IL-2 and IL-15, than to IL-7. Moreover, the study showed irreconcilable structural differences between IL-7 and all the remaining cytokines signalling through the γc receptor ( IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21).

Interleukin 10