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.
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
Antiviral proteins also involved with innate immunity and with antiproliferative effects
Variety of actions, many are pro-inflammatory
Colony stimulating factors (CSF)
Proliferation and differentiation of hematopoetic progenitor cells
Tumor necrosis factors (TNF)
Pro-inflammatory molecules that activate cytotoxic T cells
Regulate chemotaxis and recruitment of lymphocytes, many are pro-inflammatory
Note: partially adapted from Tisoncik et al. (2012) and updated with links to Bio-Rad product pages.
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.
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).
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.
Bio-Rad has a wide selection of paired antibodies for capture and detection in ELISA, along with reagents required to perform the analysis:
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