Cytokines and Chemokines

Introduction

Inflammatory and immune responses are carefully controlled, orchestrated events requiring fast and direct activation of multiple signaling pathways and recruitment of immune cells. These responses are made possible by cytokines, small molecules that act as chemical messengers to coordinate the immune response, and by chemokines, a subset of cytokines that induce cell migration.


What Are Cytokines?

Cytokines are a large, diverse group of molecules that regulate cellular activities such as growth, survival, and differentiation. They are produced by immune and nonimmune cells, and act by binding to surface receptors on target cells and triggering changes in gene expression (Ramani et al. 2015). Cytokines can be pro- or anti-inflammatory but have a variety of more specific roles; some of the main classes of cytokine and their roles can be found in Table 1 (Tisoncik et al. 2012).

Multiple cell types can secrete a particular cytokine, and cytokines can act on multiple different tissues. They may also be produced in a cascade, with one cytokine stimulating a cell to produce another cytokine, and so on (Zhang et al. 2009). Different types of infection will initiate production of different subsets of cytokine; for example, viral infections will trigger production of antiviral interferons. The cytokine network allows impressive flexibility and redundancy during inflammation and immunity.

Table 1. Some of the main types of cytokines and their roles.

Major Cytokine Class

Description

Example Cytokines

Interferons (IFN)

Antiviral proteins also involved with innate immunity and with antiproliferative effects

IFN-alpha, IFN-beta, IFN-gamma

Interleukins (IL)

Variety of actions, many are pro-inflammatory

IL-2, IL-4, IL-6, IL-18, IL-21

Colony stimulating factors (CSF)

Proliferation and differentiation of hematopoetic progenitor cells

CSF1, CSF2, CSF3, GM-CSF

Tumor necrosis factors (TNF)

Pro-inflammatory molecules that activate cytotoxic T cells

TNF-alpha, TNF-beta

Chemokines

Regulate chemotaxis and recruitment of lymphocytes, many are pro-inflammatory

CCL2, CCL5, CCL17, CXCL5,
CXCL-9, CXCL10, CCL25

Note: partially adapted from Tisoncik et al. (2012) and updated with links to Bio-Rad product pages.


What Are Chemokines?

Chemokines are chemotactic cytokines which attract white blood cells out of the blood and into tissues at the site of infection or injury, and are also involved with movement of white blood cells from tissues into the blood. They fulfil their roles by signaling through cell surface G protein-coupled heptahelical chemokine receptors (Hughes and Nibbs 2018). There are two main groups of chemokines, those that maintain homeostasis and those that induce inflammation (Zlotnik et al. 2011). They can also regulate lymphoid organ development and T cell differentiation.


Cytokines and Chemokines in Disease

Although cytokines and chemokines work to protect us, they can also cause us harm.

Cytokines play pivotal roles in autoimmune disease. Excessive pro-inflammatory cytokine responses or inadequate action of anti-inflammatory cytokines contributes to self-directed inflammation (Moudgil and Choubey 2011). TNF-α, for example, is heavily involved with the pathogenesis of rheumatoid arthritis; an autoimmune disease during which an imbalance between inflammatory and anti-inflammatory cytokines causes joint inflammation through T cell activation (McInnes and Schett 2007). Cytokines are also involved with the development of cancer (Dranoff 2004).

Some infections can result in a disproportionate immune response known as a cytokine storm. This condition can present as systemic inflammation, multiple organ failure, and high parameters of inflammation, and can even lead to death. At a molecular level, the storm follows a characteristic pattern, with early elevation of acute response cytokines (TNF and IL-1β) and chemotactic cytokines (IL-8 and MCP-1), followed by an increase in the inflammatory mediator IL-6. Subsequently, the body produces anti-inflammatory IL-10 in an attempt to control the response, but this leads to immunoparalysis and downregulation of neutrophil and monocyte function (Tisoncik et al. 2012).

Because of their role in autoimmune and inflammatory disorders, cancer, and the cytokine storm response, modulation of cytokines may have therapeutic potential. TNF-α blockade, for example, is an effective treatment for rheumatoid arthritis (Ma and Xu 2013). An antagonist of IL-1β can be used to treat the cytokine storm caused by infection (Ye et al. 2020). Tocilizumab, a monoclonal antibody against IL-6 receptor, appears to prevent hyper-inflammation and death in COVID-19 related pneumonia (De Rossi et al. 2020).


Antibodies and Recombinant Proteins

Bio-Rad’s range of antibodies and recombinant proteins to cytokines and chemokines (and their associated receptors) come in a variety of different formats and to a wide range of target species.

These antibodies can be used for applications including flow cytometry, western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and ELISA.

Bio-Rad has a wide selection of paired antibodies for capture and detection in ELISA, along with reagents required to perform the analysis:  

  • Blocking buffers including our most popular high performance buffer; Block Ace (BUF029)
  • Coating buffers
  • Washing buffers
  • Stabilizers and diluents
  • Substrates
  • Assay diluents

Plus useful practical advice you can trust to ensure optimal results.

Please use the filters to sort the attributes in the table below, in order to find the antibody that fits your exact requirements. If you need any further assistance please do not hesitate to contact us.

Cytokines and Chemokines

    DescriptionSpecificityTargetFormatHostIsotypeClone Applications Citations Product Type Code

    References

    • De Rossi et al. (2020). Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up. EClinicalMedicine. Assessed July 28,2021.
    • Dranoff (2004). Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4, 11–22.
    • Hughes and Nibbs (2018). A guide to chemokines and their receptors. FEBS J 285, 2944–71.
    • Ma and Xu (2013). TNF inhibitor therapy for rheumatoid arthritis. Biomed Rep 1, 177–184.
    • McInnes and Schett (2007). Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7, 429–442.
    • Moudgil and Choubey (2011). Cytokines in autoimmunity: role in induction, regulation, and treatment. J Interferon Cytokine Res 31, 695–703.
    • Ramani et al. (2015). Cytokines: the good, the bad, and the deadly. Int J Toxicol 34, 355–65.
    • Tisoncik et al. (2012). Into the eye of the cytokine storm. Microbiol Mol Biol Rev 76, 16–32.
    • Ye et al (2020). The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect 80, 607–613.
    • Zhang et al. (2009). Cytokines, inflammation and pain. Int Anesthesiol Clin 45, 27–37.
    • Zlotnik et al. (2011). Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol 11, 597–606.