Inflammation Part 7: Establishing Cytokine Ranges

Establishing “normal” ranges for serum cytokines... an elusive endeavor

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

As research progresses, guidelines for cytokine evaluation are emerging though “normal versus abnormal” ranges are difficult to determine with certainty due to the dynamic nature of the cytokine response.

Variables that can affect the cytokine milieu include activating signals, cellular targets, and individual characteristics including stress, fitness, and fed versus non-fed state. Some research does suggest that certain cytokine patterns correlate with certain disease states, utilizing fluids (e.g., pleural, synovial, drainage) while other used serum levels.

For example, low levels of anti-inflammatory interleukin-13 have been observed in Alzheimer’s patients. Research suggests that production of IL-13 may be downregulated in Alzheimer’s and levels 9-18 times lower were found in patients versus healthy controls. A cut-off value for IL-13 of 9.315 pg/mL was found to have 100% sensitivity and specificity for diagnosing Alzheimer’s. [1]

Serum interleukins may also provide clues to diagnosing and monitoring lupus nephritis:

• For active lupus nephritis, cut-offs of 12.3 pg/mL (IL-6) and 19.7 pg/mL (IL-17) were proposed.
• For remission of lupus nephritis, higher cut-offs of 20.8 pg/mL (IL-6) and 27 pg/mL (IL-17) were suggested. [2]

Mayo Clinic 13 cytokine panel [3]

Reference values for Mayo’s 13 cytokine panel:

Inflammation: A focus on cytokines - Optimal Takeaways

So, our takeaways from a focus on cytokines include:

• Cytokines are messengers that are produced by, and have an effect on a wide range of cells. Many cytokines interact with each other.
• They can have pro- and anti-inflammatory effects and facilitate immune function and allergic responses.
• Prolonged, unbridled inflammation can lead to a cytokine storm.
• Many cytokines are short-lived and acute measurement and interpretation can be difficult.
• The more commonly monitored cytokines include IL-1 beta, IL-6, IL-8, and TNF-alpha
• Elevated pro-inflammatory cytokines correlate with ARDS and COVID-19

Next Up: Inflammation Part 8 - Interleukin 6

Research

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

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

[3] Mayo Clinic 13 cytokine panel. (ARUP labs) https://www.mayocliniclabs.com/test-catalog/download-setup.php?format=pdf&unit_code=75139