Cytokines

Author: Prof. Dr. med. Peter Altmeyer

Last updated on: 29.10.2020

Classification
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There are four main groups of cytokines:

Interferons (IFN)
interleukins (IL)
Colony stimulating factors (CSF)
Tumour necrosis factors (TNF), see below tumor necrosis factor-α.

General information
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Cytokines are small proteins that are often stabilized by glycosylation and intramolecular disulfide bridges. They are formed by different cell types and have autocrine, paracrine or holocrine signalling effects as messengers (transmitters). Cytokines mediate and regulate interactions between different cells, which are predominantly part of the immune system and haematopoiesis. Cytokines act in nano- to picomolar concentrations and, unlike hormones, are not stored in glands as a prefabricated protein, but are quickly re-synthesized and secreted upon stimulation. They are produced by a wide variety of cell types, but especially by lymphocytes, monocytes and macrophages. The effect can be stimulating, inhibiting, synergistic or antagonistic. They only act in certain phases of the cell cycle. Often other cytokines are released by cytokines. By cascading successive cytokine reactions, the effect is enhanced. A prerequisite for the effect of cytokines is their binding to specific receptors on the respective target cell.

Tables
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Cytokine	Abbreviation	Synonyms	Place of education	Target cells	Functions/remarks
Erythropoietin	EPO		kidney, liver	Progenitor cells of erythropoiesis	Stimulation of erythropoiesis, maturation of megakaryocytes.
Granulocyte colony stimulating factor	G-CSF		monocytes, macrophages, fibroblasts	Progenitor cells of granulopoiesis	Stimulation of granulopoiesis; acceleration of the cell cycle of stem cells, influence on infection defence and inflammation
Granulocyte-macrophage colony stimulating factor	GM-CSF		lymphocytes, macrophages, fibroblasts	Progenitor cells of granulopoiesis, monopoiesis; granulocytes, monocytes, macrophages	Stimulation of granulo-, mono-, erythro- and thrombopoiesis; mobilisation of stem cells; migration and proliferation of endothelial cells.
Interferon alpha	INF-α	Interferon-alpha; Leukocyte interferon; LeIF	Leukocytes		Immunomodulation, activation of B, T, NK cells and macrophages, stimulation of HLA class I expression.
Interferon beta	INF-β	interferon-beta; fibroblast interferon; FIF	Fibroblasts		Immunomodulation, activation of B, T, NK cells and macrophages, stimulation of HLA class I expression.
Interferon gamma	INF-γ	Interferon-gamma; immune interferon	Lymphocytes (especially NK cells and activated T cells)	including macrophages, NK cells	Immunomodulation, activation of B, T, NK cells, macrophages and granulocytes; stimulation of T and B cell differentiation; stimulation of HLA class II expression; induction of immunoglobulin Fc receptors; activation of cytotoxicity against tumor cells and antimicrobial activity of macrophages; induction of monocyte differentiation; inhibition of growth of intracellular protozoa and bacteria; stimulation of IL1 and IL2 synthesis.
interleukin-1	IL-1	Lymphocyte activating factor; LAF	Macrophages, dendritic cells, astrocytes, keratinocytes, vascular endothelial and renal mesangium cells	Antigen presenting cells, lymphocytes	Key enzyme in inflammation; activation of antigen-presenting cells, CD4 cells, cytotoxic T lymphocytes, NK cells; important role in the regulation of IL-2, IL-4, IL-6, IL-8, GM-CSF and other cytokines; key enzyme in dermatomyositis and pemphigus vulgaris.
interleukin-2	IL-2	lymphocyte mitogenic factor	activated T-cells	Macrophages, T, B, NK cells	One of the most important growth factors for CD4 and CD8 cells as well as for B cells, whose productivity it increases; stimulation of other cytokines; stimulation of the cytotoxicity of activated macrophages
interleukin-3	IL-3	multipotential colony stimulating factor; hematopoietic growth factor; mast cell growth factor	activated T-cells	Cells of the haematopoietic system	Growth factor for mast cells, among others.
interleukin-4	IL-4	B-cell growth factor; lymphocyte stimulatory factor 1	activated T-helper cells	including B cells, T cells, mast cells	Autocrine T-cell stimulating factor in the absence of IL-2; stimulation of B-cell proliferation, whereby the production of IgE (high concentration IL-4) and IgG1 (low concentration IL-4) is stimulated (IFN gamma acts antagonistically); inhibition of the formation of IgG2a; increase in the expression of MHC antigens; as a switching factor? involved in the change of Ig heavy chains in antibody production (differentiation factor); inhibition of T cell proliferation; together with IL-3 mast cell proliferation; stimulation of IgE synthesis.
interleukin-5	IL-5	T-cell-replacing factor; TRF; B- cell growth factor II; BCGF-II	activated T-helper cells	activated B cells, eosinophils	Increase in antibody production (IgM, IgG, IgA); activation and growth proliferation for eosinophils (e.g. in parasitic diseases).
interleukin-6	IL-6	B-cell differentiating factor; B-cell stimulating factor 2; BSF2	activated T cells, macrophages, fibroblasts, endothelial cells	among others leucocytes, B-cell, keratinocytes, hepatocytes	Stimulation of the development of leukocytes from haematopoietic progenitor cells; stimulation of the differentiation of B cells into antibody-producing plasma cells; growth factor for plasma cells, keratinocytes and mesangium cells; stimulation of hepatocytes for the synthesis of acute phase proteins (CRP, fibrinogen, serum amyloid A, alpha 1 antitrypsin)
interleukin-7	IL-7	Lymphopoietin 1; LP-1; pre-B cell factor	Stroma cells of the bone marrow	immature and mature B- and T- lymphocytes	Promotes the growth of lymphoid stem cells as well as pre-B cells, prothymocytes, thymocytes, CD4 and CD8 T cells; co-stimulator for mature B and T cells as well as myelotic cells.
interleukin-8	IL-8	Neutrophil activating factor 1, NAP-1	activated macrophages, synoviocytes, endothelial cells and fibroblasts	Granulocytes	Chemotaxis factor for granulocytes and their activation and migration from the bloodstream into tissue.
interleukin-9	IL-9	T-cell/mast cell growth factor P40; P40 cytokines; P40 T-cell and mast cell growth factor; TCGF III; MEA	among others T-lymphocytes (TH-2 cells), B-lymphocytes, mast cells	including mast cells, NK cells, T cells	Stimulation of the maturation of mast cells; enhancement of IgE production; stimulation of the cytotoxicity of T-killer cells and NK-cells as well as the production of IL-2, IL-4, IL-6, IL-11, IFN gamma.
interleukin-10	IL-10	Cytokine synthesis inhibitory factor; CSIF	TH1 and TH2 cells, monocytes, macrophages	TH1 cells, macrophages	Potential anti-inflammatory cytokine; inhibition of the formation of interferons, IL-1, IL-6, and TNF-alpha; stimulation of IgE synthesis.
interleukin-11	IL-11		bone marrow cells, keratinocytes	among others hematopoietic stem cells and progenitor cells of megakaryocytes	Thrombopoietic growth factor with direct stimulation of the proliferation of hematopoietic stem cells and progenitor cells of megakaryocytes; reduction of mRNA of TNF-alpha and IFN gamma in keratinocytes in psoriatic patients.
interleukin-12	IL-12	NK-cell stimulatory factor; NKSF	B cells and macrophages	T lymphocytes and NK cells	NK cell stimulation and activation; induction of the differentiation of naive helper cells into TH1 cells.
interleukin-13	IL-13	P600	TH2 cells	monocytes, B-lymphocytes, mast cells, keratinocytes, endothelial cells	Stimulation of the differentiation of monocytes into dendritic cells; stimulation of IgG, IgM and IgE synthesis; reduction of the production of proinflammatory enzymes in keratinocytes and endothelial cells.
interleukin-14	IL-14	High molecular weight B-cell growth factor; HMW-BCGF	B cells, T cells	B-cells	Stimulation of B-cell differentiation; key factor in the development of non-Hodgkin lymphomas of the B-cell type
interleukin-15	IL-15		fibroblasts, keratinocytes, endothelial cells, macrophages	T and B lymphocytes, NK cells, monocytes, eosinophils, circulating neutrophils	Synergistic effect like IL-2 in T-cell activation and proliferation.
interleukin-16	IL-16	Lymphocyte chemoattractant factor; LCF	among others keratinocytes and Langerhans cells	CD4 cells, monocytes, eosinophils	Chemotactic effect on CD4 lymphocytes, eosinophils, monocytes, among others; activation of CD4 cells together with IL-1.
interleukin-17	IL-17	Neuronal interleukin-17 related factor	predominantly CD4 cells	among others cells of the immune system and keratinocytes	Stimulation of the formation of adhesion molecules in keratinocytes (ICAM1) and IL-1 secretion in dermal endothelial cells; activation of skin fibroblasts.
interleukin-18	IL-18	IFN gamma-inducing factor	among others keratinocytes	Keratinocytes; Langerhans cells	Induction of IFN gamma and G-CSF and inhibition of IL-10 in NK cells; migration of Langerhans cells.
interleukin-19	IL-19	Melanoma differentiation associated like- protein	Monocytes	Macrophages, TH1 and TH2 cells	Anti-inflammatory cytokine; inhibition of the formation of interferons, IL-1, IL-6, and TNF-alpha as well as antigen presentation in macrophages; inhibition of the activity of TH1 and TH2 cells; stimulation of the synthesis of bcl-2 protein with effect in the apoptosis of tumor cells and cells of the immune system.
interleukin-20	IL-20		among others keratinocytes	among others keratinocytes	Regulation of inflammation of the skin.
interleukin-22	IL-22	Interleukin 10 related T-cell derived inducible factor	activated T cells and mast cells		Regulation of inflammation.
Interleukin-23	IL-23		Macrophages, dendritic cells	Memory T-cells	Key enzyme in autoimmune inflammatory reactions in the CNS.
interleukin-25	IL-25		activated T-cells	CD4 cells of the TH2 subtype	Enhancement of the expression of TH2-cell associated cytokines such as IL-4, IL-5 and IL-13.
interleukin-27	IL-27		antigen-presenting cells (especially activated monocytes and dendritic cells)	naive CD4 cells (TH0 subtype)	Induction of clonal expansion of naive CD4 cells but not of memory cells; synergistic effect with IL-12 on the induction of TH1- or NK-cell-mediated production of interferon gamma.
Thrombopoietin	TPO		Liver, kidney, spleen		Stimulation of thrombopoiesis.