Table 1 displays the biological activities and cellular sources of cytokines of immunological interest. In most cases, protein mass is given, usually for human cytokines. In some instances, a given cytokine may have biological activities in addition to those listed here or may be produced by other sources as well as the ones cited here. (Note that cytokines that are not closely identified with the immune system—e.g., growth hormone—are not listed. Also, with the exception of IL-8, chemokines are not included in this compilation.) Table 2 displays select groups of cytokines that are functionally related and Table 3 displays the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) molecules that are activated by major cytokine/cytokine receptor interactions.
Major references used for the information in this appendix:
| Cytokine; MW; Synonyms | Sources | Activity |
|---|---|---|
Interleukin 1 (IL-1) IL-1α: 17.5 kDa IL-1β: 17.3 kDa Lymphocyte-activating factor (LAF); mononuclear cell factor (MCF); endogenous pyrogen (EP) |
Many cell types, including monocytes, macrophages, dendritic cells, NK cells, and non–immune system cells such as epithelial and endothelial cells, fibroblasts, adipocytes, astrocytes, and some smooth muscle cells |
Displays a wide variety of biological activities on many different cell types, including T cells, B cells, monocytes, eosinophils, and dendritic cells, as well as fibroblasts, liver cells, vascular endothelial cells, and some cells of the nervous system. The in vivo effects of IL-1 include induction of local inflammation and systemic effects such as fever, the acute-phase response, and stimulation of neutrophil production |
Interleukin 2 (IL-2) 15–20 kDa T-cell growth factor (TCGF) |
Activated T cells |
Stimulates proliferation and differentiation of T and B cells; activates NK cells |
Interleukin 3 (IL-3) 15.1 kDa (monomer) 30 kDa (dimer) Multipotential colony-stimulating factor; hematopoietic cell growth factor (HCGF); mast-cell growth factor (MCGF) |
Activated T cells, mast cells, basophils, and eosinophils |
Growth factor for hematopoietic cells; stimulates colony formation in neutrophil, eosinophil, basophil, mast cell, erythroid, megakaryocyte, and monocytic lineages but not of lymphoid cells |
Interleukin 4 (IL-4) 15–19 kDa B cell–stimulatory factor-1 (BSF-1) |
T cells (particularly those of the TH2 subset), ILC2, mast cells, basophils, and bone marrow stromal cells |
Involved in type 2 responses. Promotes naїve T-cell differentiation to TH2 cells. Stimulates the growth and differentiation of B cells. Induces class switching to IgE. Involved in defense against worms and protozoa, as well as pathology of asthma and allergy (with IL-5, -9, and -13) |
Interleukin 5 (IL-5) 15 kDa Eosinophil differentiation factor (EDF); eosinophil colony-stimulating factor (E-CSF) |
T cells (particularly those of the TH2 subset), ILC2, mast cells, eosinophils |
Involved in type 2 responses. Induces eosinophil formation and differentiation. Stimulates B-cell growth and differentiation. Involved in defense against worms and protozoa, as well as pathology of asthma and allergy (with IL-4, -9, and -13) |
Interleukin 6 (IL-6) 26 kDa B-cell stimulatory factor 2 (BSF-2); hybridoma/plasmacytoma growth factor (HPGF); hepatocyte-stimulating factor (HSF) |
Some T cells and B cells, several nonlymphoid cells, including macrophages, bone marrow stromal cells, fibroblasts, endothelial and muscle cells, adipocytes, and astrocytes |
Regulates B- and T-cell functions; in vivo effects on hematopoiesis. Induces inflammation and the acute-phase response |
Interleukin 7 (IL-7) 20–28 kDa Pre-B-cell growth factor; lymphopoietin-1 (LP-1) |
Bone marrow and thymic stromal cells, intestinal epithelial cells |
Growth factor for T-cell, B-cell, and ILC progenitors |
Interleukin 8 (IL-8) 6–8 kDa Neutrophil-attractant/activating protein (NAP-1); neutrophil-activating factor (NAF); granulocyte chemotactic protein 1(GCP-1); CXCL8 chemokine |
Many cell types, including monocytes, macrophages, lymphocytes, granulocytes, and non–immune system cells such as fibroblasts, endothelial and epithelial cells, and hepatocytes |
Chemokine that functions primarily as a chemoattractant and activator of neutrophils; also attracts basophils and some subpopulations of lymphocytes; has angiogenic activity |
Interleukin 9 (IL-9) 32–40 kDa P40; T-cell growth factor III |
Some activated T-helper-cell subsets (TH9), ILC2 |
Involved in type 2 responses. Stimulates proliferation of T lymphocytes and hematopoietic precursors, involved in defense against worms and protozoa, and pathology of asthma and allergy, with IL-4, -5, and -13 |
Interleukin 10 (IL-10) 35–40 kDa Cytokine synthesis inhibitory factor (CSIF) |
Activated subsets of CD4+ and CD8+ T cells, macrophages, and dendritic cells |
Anti-inflammatory; antagonizes generation of the TH1 subset of helper T cells; stimulates IgA synthesis and secretion by human B cells. Enhances proliferation of B cells, thymocytes, and mast cells. Cooperates with TGF-β |
Interleukin 11 (IL-11) 23 kDa |
Bone marrow stromal cells and IL-1–stimulated fibroblasts |
Growth factor for plasmacytomas, megakaryocytes, and macrophage progenitor cells |
Interleukin 12 (IL-12) Heterodimer containing a p35 subunit of 30–35 kDa and a p40 subunit of 35–44 kDa NK cell stimulatory factor (NKSF); cytotoxic lymphocyte maturation factor (CLMF) |
Macrophages, B cells, and dendritic cells |
Induces differentiation of the TH1 subset of helper T cells; induces IFN-γ production by T cells and NK cells and enhances NK and cytotoxic T-cell activity |
Interleukin 13 (IL-13) 10 kDa |
Activated T cells (particularly those of the TH2 subset), ILC2, mast cells, and NK cells |
Involved in type 2 responses. Role in TH2 responses; up-regulates synthesis of IgE and suppresses inflammatory responses. Involved in defense against worms and protozoa, as well as pathology of asthma and some allergies |
Interleukin 14 (IL-14) 60 kDa High-molecular-weight B-cell growth factor (HMW-BCGF) |
Activated T cells |
Enhances B-cell proliferation; inhibits antibody synthesis |
Interleukin 15 (IL-15) 14–15 kDa |
Many cell types but primarily dendritic cells and cells of the monocytic lineage |
Stimulates NK-cell and T-cell proliferation and development; helps to activate NK cells |
Interleukin 16 (IL-16) Homotetramer: 60 kDa Monomer: ≈ 17 kDa Lymphocyte chemoattractant factor (LCF) |
Activated T cells and some other cell types |
Chemoattractant for CD4+ T cells, monocytes, and eosinophils. Binding of IL-16 by CD4 inhibits HIV infection of CD4+ cells |
Interleukin 17 (IL-17) 28–31 kDa CTLA-8 (cytotoxic T lymphocyte–associated antigen 8) Family members IL-17A–F |
CD4+ T cells (particularly those of the TH17 subset), ILC3, CD8+, γδ T cells, NK cells, intraepithelial lymphocytes, and some other cells |
Involved in immunity to extracellular bacteria. Promotes inflammation by increasing production of proinflammatory cytokines (IL-1, IL-6, TNF-α, G-CSF, GM-CSF) by epithelial, endothelial, and fibroblast cells, as well as chemokines that attract monocytes and neutrophils. Can also have anti-inflammatory effects in barrier tissues |
Interleukin 18 (IL-18) 18.2 kDa Interferon γ–inducing factor (IGIF) |
Cells of the monocytic lineage and dendritic cells |
IL-1 family member. Promotes differentiation of TH1 subset of helper T cells. Induces IFN-γ production by T cells and enhances NK-cell cytotoxicity |
Interleukin 19 (IL-19) Homotetramer: 35–40 kDa |
LPS-stimulated monocytes and B cells |
A member of the IL-10 family of cytokines, induces reactive oxygen species and proinflammatory cytokines, which may promote apoptosis. Promotes TH2 differentiation by inhibiting IFN-γ and augmenting IL-4 and IL-13 production |
Interleukin 20 (IL-20) 18 kDa |
Monocytes and keratinocytes |
A member of the IL-10 family of cytokines; has effects in epidermal tissues and psoriasis. Like IL-19, shown to promote TH2 differentiation |
Interleukin 21 (IL-21) 15 kDa |
Activated CD4+ T cells |
Enhances cytotoxic activity and IFN-γ production by activated NK and CD8+ T cells. Contributes to B-cell and follicular helper T cell activation in germinal centers |
Interleukin 22 (IL-22) Homodimer: 25 kDa IL-10–related T cell–derived inducible factor (IL-TIF) |
CD4+ T cells (particularly those of the TH17 subset), ILC3 cells |
A member of the IL-10 family with roles in barrier immunity and pathogenesis. Induces epithelial cell release of antimicrobial peptides and enhances tight junction integrity. Has both pro- and anti-inflammatory effects; involved in immunity to extracellular bacteria |
Interleukin 23 (IL-23) Heterodimer consisting of p40 subunit of IL-12 (35–40 kDa) and p19 (18.7 kDa) |
Activated dendritic cells and macrophages, epithelial cells of barrier tissues |
Induces TH17 and ILC3 differentiation; involved in several pathologies of barrier tissues, including psoriasis and Crohn’s disease |
Interleukin 24 (IL-24) 35–40 kDa IL-10B; melanoma differentiation–associated protein 7 (MDA7) |
Melanocytes, NK cells, B cells, subsets of T cells, fibroblasts, and melanoma cells |
Member of the IL-10 family. Induces TNF-α and IFN-γ and low levels of IL-1β, IL-12, and GM-CSF in human PBMCs. Induces selective anticancer properties in melanoma cells by inhibiting proliferation and in breast carcinoma cells by promoting apoptosis |
Interleukin 25 (IL-25) 20 kDa IL-17E; stroma-derived growth factor (SF20) |
TH2 subset of helper T cells, mast cells, basophils, eosinophils, intraepithelial lymphocytes, epithelial cells of barrier tissues |
Proinflammatory member of the IL-17 family and alarmin. Produced by epithelial cells when barriers are breached. Together with IL-33 and TSLP induces production of type 2 cytokines by TH2 and ILC2 cells; suppresses TH17 and ILC3 cytokines and eotaxin |
Interleukin 26 (IL-26) Homodimer: 36 kDa AK155 |
Subset of T and NK cells |
Member of the IL-10 family. May have similar functions to IL-20 |
Interleukin 27 (IL-27) Heterodimer (27.5 kDa) composed of EBI3 (IL-27β) and p28 (IL-27α) |
Produced by dendritic cells, macrophages, endothelial cells, and plasma cells |
Shown to induce clonal expansion of naïve CD4+ T cells, to synergize with IL-12 to promote IFN-γ production from CD4+ T cells, and to induce CD8+ T cell–mediated antitumor activity |
Interleukin 28A/B (IL-28A/B) 22.3/21.7 kDa Interferon-λ2/3 (IFN-L2/3) |
Monocyte-derived dendritic cells |
Type III interferon (with IL-29), coexpressed with IFN-β, participates in the antiviral immune response, and shown to induce increased level of both MHC class I and II; induces regulatory T-cell proliferation |
Interleukin 29 (IL-29) 22 kDa Interferon-λ1 (IFN-L1) |
Monocyte-derived dendritic cells, TH17 cells |
Type III interferon (with IL-28) that functions similarly to IL-28A/B. Gene not found in mice |
Interleukin 30 (IL-30) 28 kDa IL-27p28 |
Antigen-presenting cells |
Subunit of IL-27 heterodimer; functions same as IL-27 |
Interleukin 31 (IL-31) 18 kDa |
Mainly activated TH2 T cells; can be induced in activated monocytes |
Proinflammatory and may be involved in recruitment of polymorphonuclear cells, monocytes, and T cells to a site of skin inflammation; also regulates hematopoietic progenitors |
Interleukin 32 (IL-32) 27 kDa NK4 |
Activated NK cells and PBMCs |
IL-1 family member. Proinflammatory cytokine, has mitogenic properties, induces TNF-α and IL-8 expression |
Interleukin 33 (IL-33) 31 kDa Nuclear factor in high endothelial venules (NF-HEV) |
Epithelial cells of barrier tissues; high endothelial venule and smooth muscle cells |
IL-1 family member and alarmin produced by epithelial cells when barriers are breached. Together with IL-25 and TSLP induces TH2 cytokine production by T cells, mast cells, eosinophils, and basophils |
Interleukin 34 (IL-34) 27.5 kDa |
Many cell types |
Promotes growth and development of myeloid cells |
Interleukin 35 (IL-35) |
Regulatory T cells |
IL-12 family member. Induces and activates regulatory T cells. Suppresses inflammatory responses |
Interleukin 36α, β, γ (IL-36α, β, γ) ?18 kDa |
Dendritic cells, monocytes, T cells, epithelial cells of barrier tissues |
IL-1 family members. Induce dendritic cells to produce proinflammatory cytokines and to express MHC class II, CD80, and CD86. Induce T cells to produce IFN-γ, IL-4, and IL-17; involved in skin inflammation |
Interleukin 37 (IL-37) 24 kDa |
Monocytes, macrophages, dendritic cells, epithelial cells |
IL-1 family member. Inhibits innate immunity and inflammatory responses |
APRIL (a proliferation-inducing cytokine) 27 kDa Tumor necrosis factor ligand superfamily member 13 (TNFSF13) |
T cells, monocytes, macrophages, and dendritic cells |
Member of the TNF family. Promotes B- and T-cell proliferation. Induces class switch recombination to IgA |
BAFF (human B-cell–activating factor) 18 kDa BLyS (B-lymphocyte stimulator); tumor necrosis factor ligand superfamily member 13B (TNFSF13B); TALL-1 (TNF and apoptosis ligand-related leukocyte-expressed ligand 1) |
T cells, monocytes, macrophages, and dendritic cells |
Member of the TNF family, occurs in membrane-bound and soluble form. Promotes B-cell differentiation and survival factor for immature B cells. Promotes activation and proliferation of mature B cells |
Cardiotrophin-1 (CT-1) 21.5 kDa |
Many cell types, including heart and skeletal muscle |
A member of the IL-6 family shown to stimulate hepatic expression of the acute-phase proteins; induces cardiac myocyte hypertrophy; increases monocyte adhesion; involved in metabolic syndrome |
Ciliary neurotrophic factor (CNTF) 24 kDa Membrane-associated neurotransmitter stimulating factor (MANS) |
Schwann cells and astrocytes |
A member of the IL-6 family that induces the expression of acute-phase proteins in the liver and has been shown to function as an endogenous pyrogen. Also shown to function in ontogenesis and promote survival and regeneration of nerves |
Granulocyte colony-stimulating factor (G-CSF) 22 kDa |
Bone marrow stromal cells and macrophages |
Essential for growth and differentiation of neutrophils |
Granulocyte-macrophage colony-stimulating factor (GM-CSF) 22 kDa |
T cells, macrophages, fibroblasts, and endothelial cells |
Growth factor for hematopoietic progenitor cells and differentiation factor for granulocytic and monocytic cell lineages |
Macrophage colony-stimulating factor (M-CSF) Disulfide-linked homodimer of 45–90 kDa Colony-stimulating factor 1 (CSF-1) |
Many cell types, including lymphocytes, monocytes, fibroblasts, epithelial cells, and others |
Growth, differentiation, and survival factor for macrophage progenitors, macrophages, and granulocytes |
Interferon alpha (IFN-α) 16–27 kDa Type 1 interferon; leukocyte interferon; lymphoblast interferon |
Cells activated by viral and other microbial components: macrophages, dendritic cells, and lymphocytes, virus-infected cells |
Induces resistance to virus infection. Inhibits cell proliferation. Increases expression of MHC class I molecules on nucleated cells |
Interferon beta (IFN-β) 22 kDa Type 1 interferon; fibroblast interferon |
Cells activated by viral and other microbial components: fibroblasts, dendritic cells, and some epithelial cells, virus-infected cells |
Induces resistance to virus infection. Inhibits cell proliferation. Increases expression of MHC class I molecules |
Interferon gamma (IFN-γ) Monomer: 17.1 kDa Dimer: 40 kDa Type 2 interferon; immune interferon; macrophage-activating factor (MAF); T-cell interferon |
TH1 cells, ILC1 cells including NK cells, and some CD8+ T cells |
The key type 1 cytokine. Supports TH1 differentiation, induces class switching to IgG subclasses. Activates macrophages and induces MHC class II expression. Weak antiviral and antiproliferative activities |
Interferon lambda (IFN-λ) Same as IL-28 and IL-29 (type 3 interferon) |
||
Leukemia inhibitory factor (LIF) 45 kDa Differentiation-inhibiting activity (DIA); differentiation-retarding factor (DRF) |
Many cell types, including T cells, cells of the monocytic lineage, fibroblasts, liver, and heart |
A member of the IL-6 family. Major experimental application: keeps cultures of ES cells in undifferentiated state to maintain their proliferation. In vivo, in combination with other cytokines, promotes hematopoiesis, stimulates acute-phase response of liver cells, affects bone resorption, enhances glucose transport and insulin resistance, alters airway contractility, and causes loss of body fat |
Lymphotoxin alpha (LT-α) 25 kDa Tumor necrosis factor beta (TNF-β); cytotoxin (CTX); differentiation-inducing factor (DIF); TNF ligand superfamily member 1 (TNFSF1) |
Activated T cells, B cells, ILC1 cells, including NK cells, macrophages, virus-infected hepatocytes |
Cytotoxic for some tumor and other cells. Required for development of lymph nodes and Peyer’s patches and for formation of splenic B- and T-cell zones and germinal centers. Induces inflammation. Activates vascular endothelial cells and induces lymphangiogenesis. Required for NK-cell differentiation |
Macrophage migration inhibitory factor (MIF) Monomer: 12 kDa; forms biologically active multimers |
Small amounts by many cell types; major producers are activated T cells, hepatocytes, monocytes, macrophages, and epithelial cells |
Activates macrophages and inhibits their migration |
Oncostatin M (OSM) 28–32 kDa Onco M; ONC |
Activated T cells, monocytes, and adherent macrophages |
Many functions, including inhibition of growth of tumor cell lines; regulation of the growth and differentiation of cells during hematopoiesis, neurogenesis, and osteogenesis. Shown to enhance LDL uptake and also stimulates synthesis of acute-phase proteins in the liver |
Stem-cell factor (SCF) 36 kDa Kit ligand (kitL); steel factor (SLF) |
Bone marrow stromal cells, cells of other organs such as brain, kidney, lung, and placenta |
Roles in development of hematopoietic, gonadal, and pigmental lineages; active in both membrane-bound and secreted forms |
Thrombopoietin (THPO) 60-70 kDa Megakaryocyte colony-stimulating factor; thrombopoiesis-stimulating factor (TSF) |
Liver, kidney, and skeletal muscle |
Megakaryocyte lineage–specific growth and differentiation factor that regulates platelet production |
Thymic stromal lymphopoietin (TSLP) 140 Da |
Epithelial cells of barrier tissues, basophils |
With IL-25 and IL-33 acts as an alarmin produced when epithelial barriers are breached. Acts on dendritic cells and CD4+ T cells to induce type 2 cytokine production by TH2 and ILC2 cells; supports B-cell proliferation and differentiation |
Transforming growth factor beta (TGF-β) ≈ 25 kDa Differentiation-inhibiting factor |
Some T cells (especially TREGs), macrophages, platelets, and many other cell types |
Inhibits growth, differentiation, and function of a number of cell types, including T and B cells, ILCs, and monocytes/macrophages. Inhibits inflammation and enhances wound healing. Induces class switching to IgA |
Tumor necrosis factor alpha (TNF-α) 52 kDa Cachectin; TNF ligand superfamily member 2 (TNFSF2) |
Monocytes, macrophages, and other cell types, including activated T cells, NK cells, neutrophils, and fibroblasts |
Strong mediator of inflammatory and immune functions. Regulates growth and differentiation of a wide variety of cell types. Cytotoxic for many types of transformed and some normal cells. Promotes angiogenesis, bone resorption, and thrombotic processes. Suppresses lipogenic metabolism |
Tumor necrosis factor beta (TNF-β) Same as lymphotoxin-α |
| Group | Cytokine Members | Function |
|---|---|---|
| Type 1 cytokines | IL-2, IFN-γ, IL-12, TNF-β (LT-α) | Regulate response to invasion by intracellular organisms (viruses, intracellular bacteria) |
| Type 2 cytokines | IL-4, IL-5, IL-9, IL-13, and sometimes IL-10 | Regulate response to worms and other extracellular pathogens |
| Type 17 cytokines | IL-22, IL-17, GM-CSF | Promote immune-mediated diseases |
| Proinflammatory cytokines | IL-1, IL-6, TNF-α, as well as some type 1 and type 2 cytokines | Mediate inflammatory response |
| Anti-inflammatory cytokines | IL-10, TGF-β | Secreted by regulatory T cells and typically inhibit inflammation |
| Cytokines that act as alarmins | IL-25, IL-33, TSLP | Alert the immune system to cell damage and/or stress |
| Antiviral cytokines | IFN-α, IFN-β | Enhance antiviral responses |
| Hematopoietic cytokines | IL-3, IL-7, IL-9, IL-11, G-CSF, M-CSF, GM-CSF | Regulate maturation of red and white blood cells |
| Cytokine Receptor | Janus Kinase | STAT |
|---|---|---|
IFN-α/-β |
JAK1, Tyk 2* |
STATs 1 and 2 |
IFN-γ |
JAK1, JAK2 |
STAT1 |
IL-2 |
JAK1, JAK3 |
Mainly STATs 3 and 5; also STAT1 |
IL-4 |
JAK1, JAK3 |
Mainly STAT6; also STAT5 |
IL-6 |
JAK1, JAK2 |
STAT3 |
IL-7 |
JAK1, JAK3 |
STATs 5 and 3 |
IL-12 |
JAK2, Tyk2 |
STATs 2, 3, 4, and 5 |
IL-15 |
JAK1, JAK3 |
STAT5 |
IL-21 |
JAK1, JAK3 |
Mainly STATs 1 and 3; also STAT5 |