Inflammation Part 6: Cytokine Biomarkers

Cytokine Biomarkers

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The ODX Inflammation Series

1. Inflammation Part 1 - The Fire Inside - Overview
2. Inflammation Part 2 - The Fire Inside - "Inflammaging"
3. Inflammation Part 3 - A Focus on Cytokines
4. Inflammation Part 4 - Cytokines & Their Functions
5. Inflammation Part 5 - The Cytokine Storm
6. Inflammation Part 6 - Cytokine Biomarkers
7. Inflammation Part 7 - Establishing Cytokine Ranges
8. Inflammation Part 8 - Interleukin 6
9. Inflammation Part 9 - Interleukin 10
10. Inflammation Part 10 - The IL-6 : IL-10 Ratio
11. Inflammation Part 11 - Resolution & Intervention

Inflammatory cytokines, as well as inflammatory proteins (e.g., CRP, SAA), and abnormal activation of certain enzymes (e.g., COX-2, SOD, glutathione peroxidase/GPx, iNOS), may serve as biomarkers of disease presence and progression in inflammatory disorders such as infection, cardiovascular disease, and endothelial disfunction. [1]

Clinical measurement of serum cytokines may provide a glimpse into the eye of the cytokine storm. However, some cytokines are short-lived and may be difficult to measure and monitor even though their effects have longevity. Also, once collected for analysis, cells can continue to produce cytokines and cytokines can degrade, stimulate, or inhibit other cytokines in the specimen vial. Still, obtaining and monitoring cytokine concentrations may be useful in [2]

• Assessing immune function and response
• Assessment of risk of developing secondary disease
• Tumor markers for leukemia, lymphoma, and breast cancer
• Monitoring progression of AIDS and inflammatory diseases (e.g., rheumatoid arthritis)
• Monitoring cytokine or anti-cytokine therapy

Examples of pro- versus anti-inflammatory cytokines [3]

Laboratory assay panels may comprise several cytokines and include [4]

• Tumor Necrosis Factor alpha
• Interleukin 2
• Interleukin 2 Receptor (CD25), Soluble
• Interleukin 12
• Interferon gamma
• Interleukin 4
• Interleukin 5
• Interleukin 10
• Interleukin 13
• Interleukin 17
• Interleukin 1 beta
• Interleukin 6
• Interleukin 8

The more commonly monitored cytokines include IL-1 beta, IL-6, IL-8, and TNF-alpha for monitoring chronic inflammation: [5]  

• Interleukin-1 beta (IL-1β) One of the key mediators of the inflammatory response to physical stress. Higher levels are associated with anxiety, panic disorders, and cardiovascular risk.
• Interleukin-6 (IL-6) - Elevated IL-6 may occur in different conditions including chronic infections, autoimmune disorders, certain cancers, and Alzheimer’s disease.
• Interleukin-8 (IL-8) - Elevated blood levels of IL-8 are associated with rheumatoid arthritis, tumor development, and Hepatitis C.
• Tumor necrosis factor alpha (TNF-α) - TNF-α is a growth factor for immune cells and osteoclasts, the cells that break down bone. It may be elevated in chronic infections, certain cancers, and Hepatitis C.

More complete and complex arrays may be available for research purposes. [6]

Next Up: Inflammation Part 7 - Establishing Cytokine

Research

[1] Chen, Linlin et al. “Inflammatory responses and inflammation-associated diseases in organs.” Oncotarget vol. 9,6 7204-7218. 14 Dec. 2017.

[2] Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference - E-Book. Elsevier Health Sciences. Kindle Edition.

[3] Monastero, Rebecca N, and Srinivas Pentyala. “Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels.” International journal of inflammation vol. 2017 (2017): 4309485. 

[4] Quest Diagnostics Serum Cytokine Panel 13. 

[5] Life Extension Cytokine Panel Blood. Retrieved December 4, 2020 from https://www.lifeextension.com/lab-testing/itemlccyt/cytokine-panel-blood-test

[6] Human Cytokine Array/Chemokine Array 71-Plex Panel. Eve Technologies from https://www.evetechnologies.com/product/human-cytokine-chemokine-71-plex-panel-hd71/