Inflammation Part 10: The IL-6: IL-10 Ratio

Ratio of IL-6 to IL-10

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

Research suggests that evaluating the ratio of IL-6 to IL-10 may be more clinically useful than measuring either cytokine alone.

Depression is recognized as a pro-inflammatory disorder and significantly lower IL-10 and significantly higher IL-6:IL-10 ratios have been observed in depressed patients (median 2.93 versus 1.08 in controls). [1] A meta-analysis of 11 studies (total 101,950 participants) revealed a 1.4 increase in likelihood of depression or depressive symptoms for those on a pro-inflammatory versus an anti-inflammatory diet such as the Mediterranean diet. [2]

In children hospitalized with pneumonia, the ratio of IL-6:IL-10 was instrumental in determining severity and prolongation of disease. [3]

Evaluation of the IL-6 to IL-10 ratio has been used to predict severity of injury in trauma patients. Early IL-6:IL-10 ratio of 3.11 correlated significantly with severity of injury and APACHI II scores .[4]

Calculation of the ratio of IL-6:IL-10 was integrated into the “Dublin-Boston score” used to determine severity of infection for hospitalized COVID-19 patients. Both the day four change in IL-6:IL-10 ratio as well as the linear Dublin-Boston score were more valuable in predicting clinical outcome at day seven than measuring IL-6 alone. Each 0.1 unit increase in IL-6:IL-10 ratio day 1-4 increased the odds of a more severe clinical outcome. [5]        

Inflammation: Focus on IL-6 and IL-10 - Optimal Takeaways

So, our optimal takeaways for IL-6 and IL-10 include:

• Monitoring of IL-6 is becoming more common in clinical care.
• Pro- versus anti- inflammatory effects of IL-6 depend on its signaling interactions with cell receptors. Blocking all effects of IL-6 can be detrimental.
• Pro-inflammatory roles of IL-6 include facilitation of the acute phase response and it is considered a marker of inflammation.
• Chronically elevated IL-6 is associated with pollution, cardiovascular disease, diabetes, cancer, lupus, anemia, sepsis, and COVID-19.
• Anti-inflammatory regulatory effects of IL-6 include maintenance of body temperature, bone health, brain function, and homeostasis
• IL-10 supports wound healing and resolution of ARDS, and helps control inflammation, autoimmune responses, and angiogenesis.
• Vitamin D promotes IL-10 production.
• The ratio of IL-6 to IL-10 can provide clues to severity of inflammation and disease.

Next Up: Inflammation Part 11 - Resolution & Intervention

Research

[1] Dhabhar, Firdaus S et al. “Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression.” Journal of psychiatric research vol. 43,11 (2009): 962-9. 

[2] Tolkien, Katie et al. “An anti-inflammatory diet as a potential intervention for depressive disorders: A systematic review and meta-analysis.” Clinical nutrition (Edinburgh, Scotland) vol. 38,5 (2019): 2045-2052. 

[3] de Brito, Rita de Cássia Coelho Moraes et al. “The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia.” BMC pulmonary medicine vol. 16,1 170. 1 Dec. 2016.

[4] Taniguchi, T et al. “The ratio of interleukin-6 to interleukin-10 correlates with severity in patients with chest and abdominal trauma.” The American journal of emergency medicine vol. 17,6 (1999): 548-51. 

[5] McElvaney, Oliver J et al. “A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19.” EBioMedicine, vol. 61 103026. 8 Oct. 2020.