How Cytokine Release Assays Work in Predictive Immunotoxicology

Pharmaceutical toxicology has grown radically in recent decades, especially in the area of cytokines. These small signalling proteins are involved in inflammatory responses and are intrinsically linked to the pathophysiology of numerous diseases. Cytokine production occurs in various cells and tissues, including lymphocytes, macrophages, peripheral nerve tissue, polymorphonuclear leukocytes, and helper T cells. They are produced both locally and transiently following immune system activation when they act as molecular messengers that control the amplitude and duration of innate immunity responses.

Given their implicit involvement in immune cell activation, cytokines can act as critical immune response markers when studying myriad diseases. They are subsequently the central focus of enormous research efforts in the pharma industry, specifically in the growing field of predictive immunotoxicology.

This blog post will delve deeper into how cytokine levels are screened using cytokine release assays (CRAs) and the role that CRAs play in predictive immunotoxicology.

What are Cytokine Release Assays Used for?

Cytokine release assays are preclinical in vitro assays used to measure blood cytokine levels in whole blood samples or peripheral blood mononuclear cells (PBMCs) after target cells have been stimulated with a candidate molecule. We say “candidate” as the cytokine release assay is most commonly used to screen the efficacy of novel molecules in provoking an immune response–a critical metric in new drug discovery. 

Cytokines can have both positive and negative effects on the immune system, leading to what one symposium referred to as the “good, bad, and ugly” effects of cytokines. On one hand, cytokines play an important role in helping the immune system to respond to diseases and infections, leading to “good” effects. However, an overproduction of cytokines can lead to systemic inflammation and immunotoxicity, leading to “bad” effects. In some cases, cytokines can also have both positive and negative effects, leading to what is referred to as “ugly” effects.

Acute inflammation and chronic inflammation are two interesting examples of the complex mechanisms of cytokines in action. Both are closely related to antigen presentation and regulatory T cells:

  • Acute inflammation is a rapid response to infection or injury characterized by the quick production and release of cytokines and other signaling molecules. This response is crucial for activating adaptive immunity, which involves the production of specific immune cells that recognize and eliminate pathogens and other foreign substances. Regulatory T cells play a critical role in controlling and modulating the immune response, helping to prevent overactive or chronic inflammation. 
  • Chronic inflammation is a persistent immune response that can occur due to ongoing exposure to pathogens or other stimuli. Chronic inflammation can contribute to the development of various diseases and conditions, including autoimmune disorders, cancer, and other chronic issues. 

The interaction between acute and chronic inflammation, antigen presentation, and regulatory T cells is complex and not fully understood. Still, it is a critical area of research in the field of immunology and predictive immunotoxicology. 

Numerous assay platforms are available to predictive immunotoxicologists exploring the impact of novel active pharmaceutical ingredients (APIs) in preclinical settings. Cytokine release assays are used to screen the response of many immune cell targets in different samples. For example, investigative efforts may use CRAs to identify drugs that induce acute inflammation by promoting rapid cytokine release, helping researchers to characterise the potential benefits while predicting the immunotoxicity of candidate drugs. Likewise, cytokine release assays can help identify drugs likely to promote chronic inflammation by inducing persistent changes in immune responses.

On the other hand, predictive immunotoxicology can also help identify drugs or chemicals that might promote chronic inflammation by inducing persistent changes in the immune response. This information can help to identify potential risks associated with long-term exposure to these substances and to develop strategies to mitigate these risks.

Looking for More Information?

Discover the benefits of Synexa Life Sciences’ tailored and collaborative approach to predictive immunotoxicology through our expertise in cytokine release assays. Our guiding principles of providing customized solutions to meet our clients’ unique needs, combined with our scientific knowledge, allow us to partner with you in furthering scientific development and enhancing the management and treatment of human health. Connect with us today to learn more about our innovative solutions.

References and further reading:

  1. Ramani T, Auletta CS, Weinstock D, et al. Cytokines: The Good, the Bad, and the Deadly. International Journal of Toxicology. 2015;34(4):355-365. doi:10.1177/1091581815584918
  2. Van der Meide PH, Schellekens H. Cytokines and the immune response. Biotherapy. 1996;8(3-4):243-9. doi: 10.1007/BF01877210. PMID: 8813336.


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