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Cytokines

Chapter:
Nomenclature
Author(s):

Harriet S. Meyer

Cytokines

  • … some viruses subvert the immune response by
  • producing homologs of mammalian cytokines or
  • their receptors.
  •  J. J. Oppenheim and M. Feldmann20(p7)

Cytokines are proteins or glycoproteins produced after stimulation (such as activation of immune cells) that act at short distances in very low concentrations to produce various effects, such as immune and inflammatory reactions, repair processes, and cell growth and differentiation.6,20-25 Each cytokine has multiple effects and overlaps with other cytokines, including structurally dissimilar ones, in those effects. The multiple effects (pleiotropy) are explained by the presence of cytokine receptors on a wide variety of cells, and the overlap (redundancy) by structural similarities of the intracellular portions of cytokine receptors.26

Cytokines were originally named by function. Because of their multiple and overlapping functions,20 the interleukin nomenclature27,28 was proposed to simplify terminology of this major class of cytokines and, it was hoped, subsequent regulatory immune system proteins. The more recent grouping of cytokines by receptor families and signaling pathways, however, does not necessarily correspond to previous groupings; eg, the interleukins fall into more than one family.

Cytokine Families and Subfamilies.

Molecular similarity of cytokine receptors has resulted in their grouping into families and subfamilies26:

chemokine families (see 15.8.1, Chemokines)

interleukin 1/toll-like receptors (IL-1/TLR)

platelet-derived growth factor family (PDGF)

receptor tyrosine kinases

transforming growth factor β (TGF-β) receptor serine kinase family

tumor necrosis factor (TNF)

type 1 (hematopoietins)

βc-utilizing (common cytokine receptor β chain)

γc-utilizing (common cytokine receptor γ chain)

gp130-utilizing

heterodimeric

homodimeric

type 2 (interferons; IL-10 family receptors)

heterodimeric

Cytokine signaling pathways are associated with the families and subfamilies.

Cytokine Signaling Pathways

Expansion or Origin of Term

Associated Cytokine Family

caspases

TNF

FADD

Fas-associated death domain

TNF

FAST-1

forkhead activin signal transducer

TGF-β receptor serine kinase family

IRAK

IL-1 receptor-associated kinase

IL-1/TLR

Jak1

Janus kinase 1

type 1

Jak2

Janus kinase 2

type 1

Jak3

Janus kinase 3

type 1

MyD88

myeloid differentiation marker

IL-1/TLR

NF-κB

nuclear factor–κB

IL-1/TLR

Ras/Raf/MAPK

ras protein, raf protein (see also 15.6.3, Oncogenes and Tumor Suppressor Genes), mitogen-activated protein kinases

type 1, receptor tyrosine kinases

SARA

SMAD anchor for receptor activation

TGF-β receptor serine kinase family

SMADs

mothers against decapentaplegic (dpp) signaling (MAD) in Drosophila and Sma genes from Caenorhabditis elegans29

TGF-β receptor serine kinase family

STAT1

signal transducer and activator of transcription 1

type 1

STAT2

type 1

STAT3

type 1

STAT4

type 1

STAT5

type 1

STAT5a

type 1

STAT5b

type 1

STAT6

type 1

TAK1

TGF-β–associated kinase

TGF-β receptor serine kinase family

TRADD

TNF receptor–associated death domain

TNF

TRAFs

TNF-α receptor–associated factors

TNF

TRAF6

IL-1/TLR

Tyk2

tyrosine kinase 2

type 1

The pathway terms need not be expanded, but context should be clear at first mention, eg:

the Jak1 signaling pathway

Chemokines.

See 15.8.1, Chemokines.

Colony-Stimulating Factors.

Colony-stimulating factors (CSFs) stimulate growth and differentiation of 1 or more blood cell types (neutrophils, eosinophils, monocytes/macrophages). Terms often include the letters SF, but not always (eg, interleukins 3, 4, and 5—IL-3, IL-4, IL-5—which are also CSFs). Expand CSF terms at first mention:

granulocyte-macrophage colony-stimulating factor

GM-CSF

granulocyte colony-stimulating factor

G-CSF

macrophage colony-stimulating factor

M-CSF

Hormones.

These hormones are also considered cytokines:

erythropoietin

Epo

growth hormone

GH

leptin

prolactin

PrL

thrombopoietin

Tpo

Interleukins.

A subset of cytokines were designated as interleukins in 1978 for “their ability to act as communication signals between different populations of leukocytes.”27(p2929) The interleukins have other biological effects as well. Their nomenclature was formalized in 1991.28 They are designated by number in order of discovery, eg, interleukin 1, interleukin 18, interleukin 29, but in general have no structural or functional relationship to one another. Although most have now been recognized as members of larger cytokine families, they retain their original designations. Specific interleukins are mentioned most commonly in their abbreviated form (note hyphen):

IL-1

IL-18

IL-29

The IL-1 family includes 2 forms of IL-1:

IL-1α

IL-1β

and the IL-1 receptor antagonist:

IL-1ra

Receptors for interleukins are designated, at minimum, with the interleukin name plus a capital R, eg:

IL-2R

IL-4R

Receptor names designating subtypes may be even more specific:

IL-1RI

IL-1RII

Greek letters are used for subunits (chains) of the same receptor:

IL-2Rα

IL-2Rβ

IL-6Rα

IL-6Rβ

IL-12Rβ1

IL-12Rβ2

Terms for interleukins from different species should be expanded at first mention:

human IL-2

hIL-2

mouse IL-4

mIL-4

viral IL-10

vIL-10

For terminology for therapeutic interleukins, see 15.4.13, Drugs, Nomenclature for Biological Products.

Interferons.

Interferons (IFNs) are another group of cytokines, originally discovered (and named) because of their interference with viral replication.

The type I IFNs, also known as antiviral interferons, are as follows:

IFN-α

IFN-β

IFN-λ1 (IL-29)

IFN-λ2 (IL-28A)

IFN-λ (IL-28B)

IFN-κ

IFN-ω

IFN-τ

Type II IFN, also known as immune interferon, is

IFN-γ

For terminology for therapeutic interferons, see 15.4.13, Drugs, Nomenclature for Biological Products.

Other Cytokines.

Other cytokines include the following:

Term

Abbreviation

cardiotrophin 1

CT-1

ciliary neurotrophic factor

CNTF

endothelial growth factor

EGF

FLT-3/FLT-2 ligand

FL

high mobility group box chromosomal protein 1

HMGB-1

leukemia inhibitory factor

LIF

lymphotoxin α

LTα

oncostatin M

OSM

receptor activated nuclear factor–κB ligand

RANKL

stem cell factor

SCF, c-kit ligand

transforming growth factor β

TGF-β, TGF-β1, TGF-β2, TGF-β3

tumor necrosis factor α

TNF-α

tumor necrosis factor β

TNF-β

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