An IL-6 blood test measures interleukin-6, the immune signal that tells your liver to make CRP. High levels are linked to heart disease, and drugs that block IL-6 cut CRP by up to 92% in a 2021 trial. But the test has no agreed normal range and shifts with the clock, so CRP is still the one to ask for.
This article is part of our series on [how to test for inflammation](/articles/how-to-test-for-inflammation).
How we got here
In 2000, researchers went back to blood drawn years earlier from apparently healthy men. They compared 202 who later had a heart attack with 202 matched men who did not. The men who went on to have a heart attack had more IL-6 in their blood at the start. Those in the top quarter had 2.3 times the risk of those in the bottom quarter.
At the time, IL-6 was mostly a lab word. Interleukin-6 is a cytokine: a protein that immune cells release to send messages to other cells. The body makes it promptly after an infection or a tissue injury, and then production is meant to switch off. When it keeps running, the result is chronic inflammation, and in some people autoimmune disease.
One of the places the message lands is the liver. The chain runs from a sensor inside immune cells, through a signal called IL-1, to IL-6, and on to CRP, the protein your liver makes and the one your doctor actually measures. CRP is the echo. IL-6 is the voice.
By 2014, 29 prospective studies had measured IL-6 in people and then waited. For each standard-deviation rise in IL-6, the risk of a heart attack or death from coronary disease was 25% higher. The authors said what cohort authors have to say: the findings "lend support to the inflammation hypothesis," but "further studies are needed to assess causality."
Here is the arc, study by study, from the papers we read:
| Year | Study | Design | What it found |
|---|---|---|---|
| 2000 | Healthy men followed for 6 years | Prospective, 202 heart attacks vs 202 matched controls | Top quarter of IL-6 had 2.3 times the heart attack risk |
| 2008 | OPTION trial of tocilizumab | Randomized trial, 623 people with rheumatoid arthritis | 59% improved on the higher dose vs 26% on placebo |
| 2012 | IL-6 receptor gene study | Mendelian randomization, 40 studies, 133,449 people | 5% lower odds of coronary heart disease per copy of the variant |
| 2014 | Pooled cohorts | Meta-analysis of 29 prospective studies | 25% higher coronary risk per 1-SD rise in IL-6 |
| 2016 | Time-of-day meta-analysis | 43 studies, 1,100 people | IL-6 is lowest in the morning |
| 2018 | CANTOS IL-6 analysis | Randomized trial, 4,833 people with stable atherosclerosis | IL-6 below 1.65 ng/L on treatment: 32% fewer major heart events |
| 2019 | Sample handling study | 45 healthy people, plasma vs serum | Unseparated serum IL-6 rose with warmth and time |
| 2021 | Healthy-range meta-analysis | 140 studies, 12,421 values | Pooled "normal" about 5 pg/mL; range 0 to 43.5 |
| 2021 | RESCUE trial of ziltivekimab | Phase 2 randomized trial, 264 people with kidney disease | CRP fell 77% to 92% vs 4% on placebo |
The turning point
A marker that tracks a disease is not the same as a marker that drives it. Cohorts can't tell the two apart. A gene study can.
CRP is the echo. IL-6 is the voice.From a 2021 review in Circ Res
Some people are born with a version of the IL-6 receptor gene that dampens the signal. You get your genes before diet, smoking or illness can touch them, so comparing carriers with non-carriers works like a trial nature ran for free. In 2012, a team pooled 40 studies with up to 133,449 people. Carriers had about 9% more IL-6 in the blood but about 8% less CRP, the same pattern seen in people given tocilizumab, a drug that blocks the receptor. And in 25,458 people with coronary heart disease and 100,740 without, each copy of the variant came with 5% lower odds of the disease. The authors' conclusion: IL-6 receptor signaling "seems to have a causal role" in coronary heart disease.
The drug already existed. In 2008, the OPTION trial gave tocilizumab or placebo to 623 people with moderate to severe rheumatoid arthritis. At 24 weeks, 59% on the higher dose had reached a 20% improvement in their arthritis, against 26% on placebo. Serious infections were the most common serious side effect. The drug went on to approval for rheumatoid arthritis and juvenile idiopathic arthritis.
Then came the heart trials. CANTOS gave 4,833 people with stable atherosclerosis a drug that blocks IL-1, one step upstream of IL-6, and measured IL-6 before and after. Those whose IL-6 fell below 1.65 ng/L had 32% fewer major heart events and 52% fewer deaths from heart disease over a median of 3.7 years. Those whose IL-6 stayed at or above that line got no significant benefit. The drug hit IL-1. The benefit tracked IL-6.
So the next step was an antibody against IL-6 itself, called ziltivekimab. In the RESCUE trial, 264 people with moderate to severe chronic kidney disease and an hs-CRP of at least 2 mg/L got one of three doses or placebo. At 12 weeks, CRP had fallen by 77%, 88% and 92% across the doses, against 4% on placebo, and the effect held through 24 weeks.
That is the number behind the headlines. The headlines are about the drugs.
What does a high IL-6 level mean?
It depends on when the blood was drawn, how the tube was handled, and which study's "normal" you hold it against.
A 2021 meta-analysis went looking for a reference range. It gathered 140 studies with 12,421 IL-6 values from healthy adults, but only 57 of those studies, with 3,166 values, reported numbers that could be pooled. Across them, healthy values ran from 0 to 43.5 pg/mL. The pooled average was about 5 pg/mL, and it rose by 0.05 pg/mL for every year of age. The spread between studies was large.
Time of day matters too. A 2016 meta-analysis of 43 studies, 1,100 people in all, found that IL-6 varies across the day, and the clearest feature is a trough in the morning. That is when most blood is drawn. The authors warned that studies which ignore the clock risk being confounded by it.
And the tube matters. In 45 healthy people, plasma read higher than serum from the same draw. Serum left unspun rose as it sat, and rose more in the warmth. Samples spun and separated right away stayed stable.
So a "high" IL-6 can be a real signal, an afternoon draw, or a tube that sat on a warm bench. It can also be a cold. IL-6 is produced promptly, and for a short time, in response to infections and tissue injuries. One number cannot tell you which of these you are looking at.
IL-6 vs CRP: which one should you test?
CRP, for most people, most of the time. Here is the reasoning.
CRP is made by the liver in response to IL-6, so it is a summary of the IL-6 signal, read downstream. It is also what the IL-6 drug trials used. RESCUE picked its patients by hs-CRP and judged the drug by how far CRP fell. We cover CRP's ranges in [what a normal CRP level is](/articles/what-is-a-normal-crp-level).
IL-6 does carry information CRP doesn't. In the 2000 study, the link with heart attacks held after adjusting for CRP. In CANTOS, the on-treatment IL-6 level was the number that sorted who benefited. Those are reasons for researchers to measure it, not yet reasons for a routine test. In the research we read, no decision for a person outside a trial hinged on the IL-6 number.
Where the evidence stands now
Three kinds of evidence now agree. Cohorts: more IL-6, more heart disease. Genes: less IL-6 signaling from birth, less heart disease. Trials: block the pathway and CRP falls hard, and in CANTOS the people whose IL-6 fell the most had the fewest events. A 2021 review treats IL-6 as the target and CRP as the clinical biomarker, and the IL-6 antibody is headed into a large outcomes trial.
What is missing is that finished trial. RESCUE measured blood markers over 24 weeks, not heart attacks. CANTOS blocked IL-1, not IL-6, and its IL-6 result is a secondary analysis, which its authors call "proof of concept evidence in humans." Proof of concept is not proof.
For the test itself, the gaps are practical: no agreed range, a morning trough, and a result that depends on how fast the tube was spun.
What it means today
Tick what you'll try this week. Your picks stay on this device.
you have an IL-6 result well above the range your lab lists and you also have a fever, new joint pain or swelling, or feel unwell; you take tocilizumab or another IL-6 blocker and notice signs of infection, since serious infections were the most common serious side effect in its trial; you are pregnant or breastfeeding; or you are thinking of ordering IL-6 testing on your own.
One tap. Results appear once 50 readers have voted, and the count is always real.
What's still open
The big question is the outcomes trial: does blocking IL-6 cut heart attacks in people with kidney disease and high CRP? RESCUE's authors say that trial is next. The smaller question is yours: what should a lab call normal? The best attempt so far pooled 3,166 values and still found the studies disagreed by a few pg/mL.
Until both close, the headlines belong to the drugs. The test on your lab form should still say CRP.
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How this article was made
Researched and written from 11 peer-reviewed papers. Our automated check matched every claim against the exact words of its source, confirmed every paper exists in PubMed, and found none retracted. Checked November 3, 2026. Not individually reviewed by a doctor. Photos are illustrative; the people in them are not patients or readers.
Grades run Strong, Moderate, Emerging, Early and Not supported, and the grade decides the words we may use. How we grade evidence · Medical disclaimer
Sources
- StudyPlasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.Ridker PM, Rifai N, Stampfer MJ et al. Circulation, 2000.PubMedFull paper
- Randomized trialEffect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.Smolen JS, Beaulieu A, Rubbert-Roth A et al. Lancet, 2008.PubMedFull paper
- Meta-analysisThe interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.Swerdlow DI, Holmes MV, Kuchenbaecker KB et al. Lancet, 2012.PubMedFull paper
- Meta-analysisInflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis.Kaptoge S, Seshasai SR, Gao P et al. Eur Heart J, 2014.PubMedFull paper
- ReviewIL-6 in inflammation, immunity, and disease.Tanaka T, Narazaki M, Kishimoto T Cold Spring Harb Perspect Biol, 2014.PubMedFull paper
- Meta-analysisDiurnal Variation of Circulating Interleukin-6 in Humans: A Meta-Analysis.Nilsonne G, Lekander M, Åkerstedt T et al. PLoS One, 2016.PubMedFull paper
- Randomized trialModulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS).Ridker PM, Libby P, MacFadyen JG et al. Eur Heart J, 2018.PubMedFull paper
- StudyEffects of blood sample handling procedures on measurable interleukin 6 in plasma and serum.Gong Y, Liang S, Zeng L et al. J Clin Lab Anal, 2019.PubMedFull paper
- Meta-analysisDefining IL-6 levels in healthy individuals: A meta-analysis.Said EA, Al-Reesi I, Al-Shizawi N et al. J Med Virol, 2021.PubMedFull paper
- ReviewInterleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease.Ridker PM, Rane M Circ Res, 2021.PubMedFull paper
- Randomized trialIL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial.Ridker PM, Devalaraja M, Baeres FMM et al. Lancet, 2021.PubMedFull paper
