Why we measure it

IL-6 and hsCRP measure related but distinct aspects of the inflammatory state. hsCRP reflects liver output in response to IL-6 signalling — it is a downstream readout. IL-6 is the upstream driver. In some individuals, hsCRP can be elevated while IL-6 appears normal, or vice versa, because they respond to different stimuli and operate on slightly different timescales. Measuring both provides a more complete picture of the inflammatory burden than either alone. A large prospective analysis by Danesh et al. in JAMA (2004), drawing on data from 52 prospective studies involving over 246,000 participants, established that long-term circulating IL-6 levels are strongly and independently associated with coronary heart disease risk — with effect sizes comparable to or exceeding other established inflammatory markers. Mendelian randomisation studies — which use genetic variants affecting IL-6 receptor signalling as natural experiments — have provided causal evidence for IL-6's role in atherosclerosis. The finding that IL-6 receptor blockade (used clinically for rheumatoid arthritis) significantly reduces cardiovascular events in high-risk patients further supports a causal relationship rather than mere association. Beyond cardiovascular disease, chronically elevated IL-6 is associated with insulin resistance, type 2 diabetes, sarcopenia (age-related muscle loss), depression, and multiple cancers — particularly colorectal cancer. In the context of ageing, IL-6 is one of the primary drivers of inflammageing: the chronic low-grade inflammatory state that characterises biological ageing and underlies its associated morbidities. Elevated IL-6 in older adults predicts functional decline, hospitalisation, and all-cause mortality independent of other risk factors.

Why every 3 months

Like hsCRP, IL-6 responds to lifestyle, sleep, diet, and physical activity on a timescale of days to weeks. Aerobic exercise acutely elevates IL-6 transiently — a physiologically normal response that resolves within hours — but regular physical activity training reduces resting IL-6 over months. Visceral adiposity is one of the strongest sustained drivers of elevated IL-6, as adipose tissue is a major source of IL-6 secretion. Quarterly measurement tracks whether the underlying inflammatory tone is shifting — and whether the changes are consistent or episodic. Because IL-6 sits upstream of hsCRP, movements in IL-6 that precede changes in hsCRP provide early signal that something is changing in the inflammatory state.

What movement means

There is no single authoritative clinical guideline that defines diagnostic thresholds for IL-6 in healthy adults, comparable to the ADA's HbA1c bands. Reference ranges vary significantly by laboratory assay method, population, age, and time of day of collection. The values below reflect ranges commonly observed in large population studies and referenced in the research literature — they are research reference values, not clinical diagnostic criteria set by Nexuses or any single guideline body. IL-6 is also more variable than hsCRP — it has a shorter half-life and is more sensitive to acute perturbations including recent exercise, minor infection, and circadian variation. This means the trend across multiple quarters is more informative than any single reading.

In the protocol