Welcome to part 7 of the ODX Inflammation Series. In this post, the ODX Research Team concludes its review of cytokines by exploring the "normal" ranges for serum cystokines - an elsuive endevor!
Establishing “normal” ranges for serum cytokines... an elusive endeavor
Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN
The ODX Inflammation Series
- Inflammation Part 1 - The Fire Inside - Overview
- Inflammation Part 2 - The Fire Inside - "Inflammaging"
- Inflammation Part 3 - A Focus on Cytokines
- Inflammation Part 4 - Cytokines & Their Functions
- Inflammation Part 5 - The Cytokine Storm
- Inflammation Part 6 - Cytokine Biomarkers
- Inflammation Part 7 - Establishing Cytokine Ranges
- Inflammation Part 8 - Interleukin 6
- Inflammation Part 9 - Interleukin 10
- Inflammation Part 10 - The IL-6 : IL-10 Ratio
- 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:
|
Cytokine
|
Reference Range
|
|
Tumor Necrosis Factor-alpha
|
7.2 pg/mL or less
|
|
Interleukin 2
|
2.1 pg/mL or less
|
|
Interleukin 2 Receptor Soluble
|
175.3 – 858.2 pg/mL
|
|
Interleukin 12
|
1.9 pg/mL or less
|
|
Interferon gamma
|
4.2 pg/mL or less
|
|
Interleukin 4
|
2.2 pg/mL or less
|
|
Interleukin 5
|
2.1 pg/mL or less
|
|
Interleukin 10
|
2.8 pg/mL or less
|
|
Interleukin 13
|
2.3 pg/mL or less
|
|
Interleukin 17
|
1.4 pg/mL or less
|
|
Interleukin 1 beta
|
6.7 pg/mL or less
|
|
Interleukin 6
|
2.0 pg/mL or less
|
|
Interleukin 8
|
3.0 pg/mL or less
|
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
