Lexicon
IL-6
Also known as Interleukin-6
Definition
Interleukin-6 (IL-6) is a cytokine that is elevated in chronic low-grade systemic inflammation, which is associated with cardiovascular disease and type 2 diabetes. [1] IL-6 was the first cytokine described as a myokine, produced and released by contracting skeletal muscle fibers during exercise and exerting effects in other organs. [1] Robust epidemiologic evidence, together with human genetic studies and mechanistic experiments, supports IL-6 as a central mediator of cardiovascular risk. [2]
How it works
IL-6 has a dual role: during exercise it stimulates anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits production of the pro-inflammatory cytokine TNF-alpha. [1] C-reactive protein is synthesized by the liver in response to inflammatory cytokines including IL-6, IL-1, and TNF, which is why IL-6 elevation is mirrored by a rise in CRP. [3] In aging, an elevation in IL-6 participates in a positive feedback loop with impaired vascular mitochondrial function that accelerates atherosclerosis. [4] IL-6 is a core cytokine of the SASP, secreted by senescent cell populations alongside other interleukins and matrix metalloproteinases, through which senescent cells can harm adjacent cells and drive neurodegenerative pathology [5]
Connected concepts
How it's measured
IL-6 is measured as a circulating blood cytokine, but before recent meta-analysis no normal reference values had been reported for IL-6 in the blood of healthy individuals. [6] Compared with many other markers of systemic inflammation, IL-6 is proposed as a useful and convenient marker of peripheral inflammation in older adults with comorbidities. [7]
What levels mean
In healthy adult donors a meta-analysis of over 12,000 values found reported IL-6 varied between 0 and 43.5 pg/mL, with a pooled estimate of about 5.186 pg/mL. [6] IL-6 rises with age, increasing by about 0.05 pg/mL for each additional year of age. [6] Chronic low-grade systemic inflammation is reflected by a roughly two- to threefold elevation of several cytokines, and higher IL-6 predicts frailty, lower muscle strength, and adverse cardiovascular outcomes. [1]
Community knowledge
## Inflammatory Aging Framework
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- 1.Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985) · 2005
- 2.Mehta NN, deGoma E, Shapiro MD. IL-6 and Cardiovascular Risk: A Narrative Review. Curr Atheroscler Rep · 2024
- 3.Plebani M. Why C-reactive protein is one of the most requested tests in clinical laboratories? Clin Chem Lab Med · 2023
- 4.Tyrrell DJ, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nat Rev Cardiol · 2021
- 5.Wang Y, Kuca K, You L, Nepovimova E, Heger Z, Valko M, Adam V, Wu Q, Jomova K. The role of cellular senescence in neurodegenerative diseases. Arch Toxicol · 2024
- 6.Said EA, Al-Reesi I, Al-Shizawi N, Jaju S, Al-Balushi MS, Koh CY, Al-Jabri AA, Jeyaseelan L.
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