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Overview

Cytokines are a class of biologically active low-molecular-weight polypeptides, proteins, or glycoproteins that are synthesized and secreted by immune cells (such as monocytes, macrophages, T cells, B cells, and NK cells) and non-immune cells (such as vascular endothelial cells, epidermal cells, and fibroblasts) upon stimulation. They exert a variety of biological functions, including maintaining cell survival and proliferation, inducing cell differentiation, regulating innate and adaptive immunity, and exhibiting antiviral activity.

Based on their functions, cytokines are classified into interleukins, colony-stimulating factors, interferons, the tumor necrosis factor superfamily, chemokines, growth factors, and others.

Subcategories

Colony Stimulating Factors
Colony Stimulating Factors

"Colony-Stimulating Factors (CSFs) are a class of cytokines that specifically regulate the hematopoietic system. Their name derives from their ability to stimulate bone marrow hematopoietic progenitor cells to form morphologically and functionally distinct cell colonies under in vitro culture conditions. Based on their lineage specificity, CSFs mainly include granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), among others. They serve as indispensable regulatory signals for the production, differentiation, and maturation of blood cells. CSFs have a wide range of clinical applications. Recombinant human G-CSF (e.g., filgrastim) is the standard supportive care therapy for bone marrow suppression following cancer chemotherapy, effectively increasing neutrophil counts and preventing severe infections. It is also used for donor mobilization prior to hematopoietic stem cell transplantation. M-CSF is being investigated for the treatment of bone marrow failure diseases such as aplastic anemia, and has shown potential in the field of cancer immunotherapy."

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Interleukin
Interleukin

Interleukins (ILs) are a group of small proteins secreted by immune cells (e.g., macrophages and T cells) as well as certain non-immune cells. They were originally named for their production by and action on leukocytes. To date, 41 interleukins, ranging from IL-1 to IL-41, have been identified. Acting as “signal messengers” between cells, interleukins play central roles in immune responses, inflammation, and hematopoiesis. Dysregulated expression of interleukins is associated with various diseases, including autoimmune disorders, allergies, infections, and cancers. Hence, interleukins serve as important diagnostic biomarkers and therapeutic targets.

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TGF-beta Superfamily
TGF-beta Superfamily

The transforming growth factor β (TGF-β) superfamily is the largest family of secreted growth factors, comprising multiple subfamilies, including TGF-βs, bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), activins, inhibins, and glial cell-derived neurotrophic factors (GDNFs). TGF-β signaling is initiated upon ligand binding to heteromeric complexes of type I and type II transmembrane serine/threonine kinase receptors. This binding triggers transphosphorylation of type I receptors by type II receptors, which then phosphorylate receptor-regulated Smads (R-Smads). These R-Smads associate with the co-Smad Smad4, translocate to the nucleus, and activate target gene transcription—a pathway known as canonical Smad signaling. In addition, the receptor complex can also activate non-Smad signaling pathways via interactions with receptor-interacting proteins. TGF-β superfamily members regulate diverse biological processes, including cell proliferation, differentiation, migration, adhesion, apoptosis, and extracellular matrix (ECM) production, and are closely implicated in the pathogenesis of various diseases.

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Epidermal Growth Factors
Epidermal Growth Factors

The epidermal growth factor (EGF) family is a group of growth factors with structural similarity to EGF, a potent mitogenic peptide. EGF family members include transforming growth factor-α (TGF-α), heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, betacellulin, epiregulin, epigen, and neuregulins 1–6. The biological effects of these ligands are mediated by the EGF receptor (EGFR/ErbB) tyrosine kinase family, which consists of four members: EGFR (ERBB1), ERBB2 (NEU/HER2), ERBB3, and ERBB4. Upon ligand binding, EGFRs are activated and trigger downstream signaling cascades that regulate multiple cellular processes, including proliferation, survival, and angiogenesis.

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Fibroblast Growth Factors
Fibroblast Growth Factors

Fibroblast growth factors (FGFs) are a family of structurally related polypeptide growth factors with diverse roles in regulating cell proliferation, migration, differentiation, and apoptosis. FGFs exert their functions by binding to FGF receptors (FGFRs) with heparin/heparan sulfate as a cofactor. Upon activation, FGFRs recruit specific molecules to phosphorylated tyrosine residues in the cytosolic domain, triggering multiple signaling pathways—including RAS-MAPK, PI3K-AKT, PLCγ, and STAT—and leading to specific cellular responses. The mammalian Fgf family comprises 22 genes, 18 of which encode proteins (FGF1–FGF10 and FGF16–FGF23) that signal through four highly conserved transmembrane tyrosine kinase receptors (FGFR1, FGFR2, FGFR3, and FGFR4). The FGF homologous factors (FGF11, FGF12, FGF13, and FGF14) share high sequence identity with the FGF family but do not activate FGFRs and are therefore not generally considered members of the FGF family. FGFs are highly conserved in both gene structure and amino acid sequence across vertebrate species.

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Vascular Endothelial Growth Factors
Vascular Endothelial Growth Factors

Vascular endothelial growth factors (VEGFs) are a family of secreted polypeptides that are crucial to the normal development and maintenance of the vascular and lymphatic systems. VEGF stimulates endothelial cells to degrade extracellular matrix, proliferate, migrate, and form tubes, and acts as an endothelial cell survival factor. VEGF also increases vascular permeability. The VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D (FIGF), VEGF-Es, and placenta growth factor (PlGF). VEGFs have been found in all vertebrate species examined to date and are highly conserved across species. The biological functions of the VEGFs are mediated by VEGFRs (VEGFR1, VEGFR2, and VEGFR3), a family of protein tyrosine kinase receptors, and two non-protein kinase co-receptors known as neuropilins (Neuropilin-1 and Neuropilin-2).

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Platelet-derived Growth Factors
Platelet-derived Growth Factors

Platelet-derived growth factors (PDGFs) are potent mitogenic factors that regulate cell growth and division in connective tissue and the developing nervous system. The PDGF family consists of five polypeptide chains (subunits): PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC, and PDGF-DD. The two receptors for PDGFs, PDGFRα and PDGFRβ, belong to the receptor tyrosine kinase (RTK) family. PDGFRα signaling controls gastrulation and the development of cranial and cardiac neural crest, lung, intestine, skin, kidney, skeleton, gonads, and neuroprotective tissues, whereas PDGFRβ signaling is well established in early hematopoiesis and blood vessel formation. PDGFs participate in wound healing, regulation of blood vessel tone, and maintenance of interstitial fluid pressure. PDGF signaling is also involved in the pathogenesis of various proliferative diseases, including certain tumors, atherosclerosis, restenosis, and fibrotic conditions.

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Insulin-like Growth Factors
Insulin-like Growth Factors

The insulin-like growth factor (IGF) family consists of two ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), at least six high-affinity binding proteins (IGFBPs 1–6), and a group of low-affinity IGFBP-related proteins (IGFBP-rPs). Members of the IGF family form a network of interactions both among themselves and with other growth factor families and their signaling pathways. IGFs play important roles in regulating cell proliferation, differentiation, apoptosis, and transformation.

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Others
Others

Additional cytokine and growth factor families, including Erythropoietin Family, Galectin Family, Hedgehog Family, Noggin Family, R-Spondin Family, Wnt Family, and others.

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Chemokine
Chemokine

"Chemokines are a class of small proteins with chemotactic activity, serving as the ""navigation system"" of the immune system. By binding to G protein-coupled receptors (GPCRs) on the surface of target cells, they activate intracellular signals and guide immune cells (such as leukocytes) to migrate directionally along chemokine concentration gradients. Chemokines play a central role in regulating the development, homing, and accumulation of immune cells at sites of inflammation and infection. Targeted therapies directed against chemokines and their receptors are a current research hotspot. The CCR5 antagonist (e.g., maraviroc) has been approved for the treatment of AIDS, acting by blocking the co-receptor required for viral entry. CXCR4 antagonists are used for stem cell mobilization in hematopoietic stem cell transplantation. In addition, inhibitors targeting chemokines such as CXCL8 (IL-8) and CCL2 are in various stages of clinical trials for the treatment of inflammatory diseases (e.g., psoriasis, rheumatoid arthritis) and various cancers."

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Neurotrophic Factors
Neurotrophic Factors

Neurotrophic Factors (NTFs) are a class of proteins that play a critical supportive role in the survival, growth, differentiation, and synaptic plasticity of neurons. They are primarily produced by the target tissues of neurons (such as muscles and glands). By binding to specific receptors (e.g., Trk receptors) on the neuronal surface, they are retrogradely transported to the cell body and activate downstream signaling pathways, thereby exerting their biological functions. This family is essential for maintaining the normal structure and function of the nervous system. Due to their potent neuroprotective and neurorepair functions, NTFs are a promising target for the development of therapies for neurodegenerative diseases.

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Interferons
Interferons

"Interferons (IFNs) are a group of key antiviral proteins produced by cells in response to viral infection or other stimuli. They serve as the ""alarm system"" and ""defense weapons"" of the immune system, primarily functioning by inducing surrounding cells to establish an antiviral state. The interferon family is mainly divided into two types: Type I interferons (such as IFN-α and IFN-β), whose main function is antiviral defense; and Type II interferon (IFN-γ), whose main function is immune regulation. Based on their potent antiviral and immunomodulatory functions, interferons have been developed as important biological agents for the treatment of viral diseases (such as chronic hepatitis B and hepatitis C) as well as certain cancers (such as hairy cell leukemia and melanoma)."

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Tumor Necrosis Factors
Tumor Necrosis Factors

Tumor Necrosis Factor (TNF) is a potent pro-inflammatory cytokine primarily secreted by activated macrophages and T lymphocytes. By binding to TNF receptors on the surface of target cells, it activates downstream signaling pathways (such as NF-κB and MAPK), thereby exerting a variety of biological effects. TNF not only directly induces apoptosis of tumor cells but also broadly regulates the activation, proliferation, and differentiation of immune cells, making it a central regulator of the body's inflammatory and immune responses.

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