Cytokines are typically small (5-20 kDa), signaling proteins secreted by cells that act as intercellular messengers to regulate a diverse array of biological processes. Interleukins, interferons, adipokines, chemokines, and members of the tumor necrosis superfamily are all considered to be cytokines. These proteins are produced by a variety of different cell types, including one or more of the following: adipocytes, endothelial cells, epithelial cells, fibroblasts, stromal cells, and immune cells such as T cells, B cells, innate lymphoid cells, dendritic cells, and macrophages.
Cytokines function by binding to specific cell surface receptors that promote the activation of intracellular signaling pathways, which induce responses such as proliferation, differentiation, activation, migration, effector activity, or cell death. As a result, cytokines affect nearly every biological process from embryonic development, immune responses, and wound healing, to tissue remodeling, disease pathogenesis, and aging. Cytokines play a particularly prominent role in regulating immunity and inflammatory responses following infection. They typically function to protect the host against invading pathogens by serving as cellular communication signals to amplify immune responses, but they can also have harmful effects under conditions where they are overproduced. This results in elevated circulating cytokine levels and can lead to immune cell hyperactivation characteristic of systemic inflammatory syndromes such as cytokine release syndrome or cytokine storm. Changes in the levels of specific cytokines are also associated with chronic inflammation in pathological conditions such as cancer, metabolic syndrome, diabetes, neuroinflammatory disorders, and autoimmune diseases.
Cytokines can mediate autocrine, paracrine, and endocrine signaling. Local cytokine signaling occurs through autocrine and paracrine signaling, which takes place when a cytokine secreted by a specific cell binds to its receptor on the same cell or on neighboring cells, respectively. Endocrine signaling by cytokines is thought to be less common but occurs when these molecules travel through the blood and have an effect on cells or tissues that are more distant from the cytokine-producing cell. In addition to receptors on the cell surface, many cytokines can also bind to soluble cytokine receptors, which can act as either agonists or antagonists of cytokine signaling. Since many cytokines are pleiotropic, they can have multiple different effects on different cell types.
Cytokine Products by Family
Adipokines
Adipokines
• Adipokines include inflammatory mediators, angiogenic proteins, and metabolic regulators that are secreted by cells present in the adipose tissue
• Adipokines regulate insulin signaling and may contribute to the development of metabolic disorders
Chemokines
Chemokines
• There are four chemokine subfamilies: C, CC, CXC, and CX3C chemokines
• Chemokines bind to conventional G protein-coupled seven transmembrane receptors, with some promiscuity
• Chemokines direct cell migration during development, homeostatic conditions, and inflammation
Common Receptor Beta Chain Family
Common Receptor Beta Chain Family
• Common beta-chain family members include GM-CSF, IL-3, and IL-5
• These cytokines signal through heterodimeric receptor complexes that contain the common beta-chain subunit
• Common beta-chain family cytokines regulate proliferation, differentiation, and functions of hematopoietic cell types
Common Receptor Gamma Chain Family
Common Receptor Gamma Chain Family
• Members of the common gamma-chain cytokine family include IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21
• All common gamma-chain family cytokines signal through receptors that contain the common gamma-chain subunit
• Common gamma-chain family cytokines regulate the development, survival, proliferation, differentiation, and functions of multiple immune cell types
IL-1 Family Cytokines
IL-1 Family Cytokines
• Members of the IL-1 cytokine family include IL-1 alpha, IL-1 beta, IL-1ra, IL-18, IL-33, IL-36 alpha, IL-36 beta, IL-36 gamma, IL-36Ra, IL-37, and IL-38
• All family members share a conserved beta-trefoil structure and bind to a primary IL-1 family receptor subunit, which subsequently recruits an accessory receptor
• IL-1 family cytokines play a key role in regulating inflammation
IL-6 Family Cytokines
IL-6 Family Cytokines
• Members of the IL-6 cytokine family include IL-6, IL-11, IL-27 p28/IL-30, IL-31, LIF, OSM, CLC, CNTF, CT-1, and Neuropoietin
• Most IL-6 family cytokines signal through a receptor complex that contains the gp130 signaling receptor subunit
• IL-6 family cytokines have distinct and overlapping functions, which include the induction of hepatic acute phase proteins, B cell stimulation, and metabolic and neurotrophic functions
IL-10 Family Cytokines
IL-10 Family Cytokines
• Members of the IL-10 cytokine family include IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26
• These cytokines have structural similarities and signal through heterodimeric receptor complexes with common subunits
• IL-10 has anti-inflammatory and immunosuppressive effects, while other IL-10 family cytokines are primarily involved in regulating the activities of epithelial cells to maintain tissue homeostasis
IL-12 Family Cytokines
IL-12 Family Cytokines
• The IL-12 family of heterodimeric cytokines includes IL-12, IL-23, IL-27, IL-35, and IL-39
• Each member of the IL-12 family consists of an alpha chain and a beta chain subunit, which are shared among different family members
• IL-12 family cytokines differentially regulate the activities of specific T cell subsets, and have pro- or anti-inflammatory effects
IL-17 Family Cytokines
IL-17 Family Cytokines
• Members of the IL-17 cytokine family include IL-17A, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, and IL-17F
• These cytokines have a highly conserved C-terminus containing a cysteine-knot fold structure and are secreted as dimers
• IL-17 family cytokines bind to members of the IL-17 receptor family and primarily promote pro-inflammatory immune responses
Interferons
Interferons
• Type I interferons include IFN-alpha, IFN-beta, IFN-omega, IFN-kappa, and Limitin/IFN-zeta
• IFN-gamma is the only member of the Type II interferon group
• Type III interferons include IL-28/IFN-lambda 1, IL-28A/IFN-lambda 2, IL-28B/IFN-lambda 3, and IFN-lambda 4
• Members of all of the interferon families have anti-viral, anti-proliferative, and immunoregulatory effects
M-CSF, SCF, Flt-3 L
M-CSF, SCF, Flt-3 L
• M-CSF, SCF, Flt-3 Ligand are short-chain, four-helix bundle cytokines with 4 conserved cysteines in their extracellular domains
• All three of these cytokines bind to class III receptor tyrosine kinases, leading to receptor dimerization, autophosphorylation, and activation
• M-CSF, SCF, and Flt-3 Ligand regulate the proliferation and differentiation of multiple hematopoietic cell lineages
TNF Superfamily
TNF Superfamily
• There are 19 TNF superfamily ligands and 29 receptors
• TNF superfamily ligands are homotrimers that bind to oligomeric type I or type II transmembrane receptors
• TNF superfamily members regulate apoptosis, cell type-specific responses, and multiple immune cell functions, including T cell co-stimulation, natural killer cell activation, and B cell activation
Cytokine Products by Application
R&D Systems Cytokines Are Frequently More Active than Leading Competitor’s Proteins
R&D Systems Recombinant Human Thrombopoietin/Tpo Displays Higher Activity than Leading Competitors’ Thrombopoietin Proteins. The bioactivity of R&D Systems Recombinant Human Thrombopoietin (Catalog # 288-TPE; orange line) or recombinant human Thrombopoietin/Tpo from two different competitors (green and purple lines) was assessed by measuring the ability of the proteins to stimulate proliferation of the MO7e human megakaryocytic leukemic cell line. The ED50 for this effect for R&D Systems Recombinant Human Thrombopoietin is 0.05-0.5 ng/mL, which is over 2-fold more active than the two competitors’ proteins.
Protein Characterization Using SEC-MALS Analysis
Recombinant Human IL‑10 Protein SEC-MALS. Recombinant human IL-10 (Catalog # 1064-ILB) has a molecular weight (MW) of 36.7 kDa as analyzed by SEC-MALS, suggesting that this protein is a homodimer. MW may differ from predicted MW due to post-translational modifications (PTMs) present (i.e. Glycosylation).
SEC-MALS Data | Result |
Retention Time | 17.9-18.5 min |
MW-Predicted (Monomer) | 19.0 kDa |
MW-MALS | 36.7 kDa |
Polydispersity | 1.002 |
System Suitability: BSA Monomer 66.4 ± 3.32 kDa | Pass |
R&D Systems Cytokines Are Rigorously Tested to Ensure Lot-to-Lot-Consistency
Lot-to-Lot Consistency Testing of Recombinant Human SCF/c-kit Ligand. Two independent lots of Recombinant Human SCF/c-kit Ligand (R&D Systems, Catalog # 11010-SC) were tested for their ability to stimulate the proliferation of TF-1 human erythroleukemic cells. The ED50 for this effect is 1-5 ng/mL. Each trace on the graph represents Recombinant Human SCF/c-kit Ligand from a different manufacturing run, demonstrating the lot-to-lot consistency of the protein.
Lot-to-Lot Consistency Testing of Recombinant Human Flt-3 Ligand. Two independent lots of Recombinant Human Flt-3 Ligand (R&D Systems, Catalog # 308-FKE) were tested for their ability to stimulate the proliferation of BaF3 mouse pro-B cells transfected with mouse Flt-3. The ED50 for this effect is 0.2-1 ng/mL. Each trace on the graph represents Recombinant Human Flt-3 Ligand from a different manufacturing run, demonstrating the lot-to-lot consistency of the protein.
Featured Cytokine Products
Animal-Free Recombinant Proteins
Animal-Free Recombinant Proteins
Ensure a seamless transition from preclinical research into clinical manufacturing by starting your preclinical experiments with our Animal-Free RUO proteins. R&D Systems Animal-Free RUO proteins are produced in dedicated animal-free laboratories and are manufactured using the same systems as our Animal-Free GMP-Grade proteins.
GMP-grade Proteins
GMP-grade Proteins
We produce our own GMP cytokines and growth factors for use as ancillary reagents in ex vivo cell manufacturing processes. GMP-grade proteins come with extensive documentation to provide cell therapy researchers with a consistent, transparent, fully traceable source of reagents. Request a GMP Protein Sample.
Bulk Proteins
Bulk Proteins
If your experiments require large quantities of a particular protein, contact us for a bulk quote. We have the capacity and the expertise to scale up the production of any protein to meet your needs, and we offer economical pricing on bulk orders.
Featured Cytokine Resources
Cytokine Signaling Pathways
Cytokine Signaling Pathways
Cytokines activate a diverse array of intracellular signaling pathways that can induce processes such as cell proliferation, differentiation, migration, and cell death. Explore the signaling pathways that are activated by different cytokine families, the primary target cells that they affect, and the biological effects that they mediate using our interactive signaling pathways.
Chemokine Superfamily Poster
Chemokine Superfamily Poster
Chemokines and their receptors control cell migration during both homeostasis and inflammation and are associated with a diverse array of pathological conditions. Learn more about chemokine ligand-receptor interactions, chemokine signaling pathways, and chemokine receptors implicated in the pathogenesis of chronic inflammatory and autoimmune diseases with our Chemokine Superfamily poster.
Cytokines and Proteins User's Guide eBook
Cytokines and Proteins User's Guide eBook
Download this guide to learn about the different applications for cytokines in cell biology research. From cell culture and lineage differentiation to antibody and immunoassay development, this guide highlights how recombinant proteins are being utilized in diverse research areas.
Additional Cytokine-Related Products and Services
Cell Culture Reagents
Cell Culture Reagents
Browse our complete collection of products for cell culture. We offer a comprehensive range of reagents to promote robust cell growth, including media and supplements, FBS, basement membrane extracts, and custom cell culture services.
Immunoassays for Cytokine Detection
Immunoassays for Cytokine Detection
From our complete, ready-to-use Quantikine™ ELISA Kits to our multiplex Luminex® Assays and fully automated Simple Plex™ Assays, you can count on our immunoassays to deliver accurate, reproducible, high-quality data for every experimental sample that you test.
Custom Protein Services
Custom Protein Services
For more specialized requests, contact our custom protein services team. Whether you are looking for a different formulation, incorporation of a non-standard label, or a specific mutated version of a protein, we have the capabilities and the team to develop the protein that you need.
Background Information on Cytokines
Cytokine are grouped into large families based on structural similarities and the specificities and composition of their receptor complexes. These families include the four helix bundle cytokines, beta-trefoil cytokines that signal through immunoglobulin superfamily receptors, cysteine-knot cytokines, chemokines, and the TNF superfamily cytokines. The four-helix bundle cytokines are further subdivided into ligands for the class I and class II cytokine receptor families. The ligands for the class I cytokine receptors share a four alpha-helical bundle structure that is arranged in an up-up-down-down topology and are subdivided into short-chain and long-chain cytokines. Short-chain cytokines include the common beta-chain and common gamma-chain family cytokines, IL-13, and TSLP. M-CSF, IL-34, Flt-3 Ligand, and SCF are also short-chain four helix bundle cytokines, but these cytokines signal through class III receptor tyrosine kinases. Long-chain cytokines of the class I cytokine receptor family include the IL-6 family cytokines, G-CSF, erythropoietin, thrombopoietin, growth hormone, prolactin, and leptin. Ligands for the class II cytokine receptor family consist of the IL-10 family cytokines, along with the type I, type II, and type III interferons. These cytokines have a common structure with six alpha-helices and are expressed as monomers or homodimers. IL-1 family cytokines are classified as beta-trefoil superfamily cytokines that signal through immunoglobulin superfamily receptors, while the IL-17 family cytokines belong to the cysteine-knot superfamily and bind to members of the IL-17 receptor family.
Chemokines are divided into four subfamilies: the C, CC, CXC, and CX3C chemokines. The subfamily designation is based on the number and spacing of conserved cysteine residues located in the amino-terminus of the protein. In addition, chemokines are classified as homeostatic, inflammatory, or dual-functioning, based on their functions and expression patterns. All chemokines bind to seven transmembrane G protein-coupled receptors (GPCRs) to activate downstream signaling pathways. The chemokine system is complex in that many chemokine receptors can be activated by more than one chemokine, and many different cell types express more than one chemokine receptor at one time, making it difficult at times to discern the role of one chemokine versus another in a particular context.
Tumor necrosis factor (TNF) superfamily ligands are characterized by a stalk that connects the transmembrane domain to a core region that contains a domain known as the TNF homology domain (THD), the hallmark structure of TNF family ligands. The THD is an anti-parallel beta-pleated sheet sandwich with a “jelly-roll” topology. Receptors for TNF family ligands are oligomeric, type I or type II transmembrane proteins that contain multiple extracellular cysteine-rich domains. Many of the TNF superfamily receptors also contain intracellular death domains, which interact with other death domain-containing proteins to initiate the extrinsic pathway of caspase activation, following ligand binding. Other TNF superfamily proteins regulate cell type-specific responses and immune cell functions, including T cell co-stimulation, natural killer cell activation, and B cell activation.