Interleukin-6, Serum

CPT: 83529
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Expected Turnaround Time

2 - 4 days

Related Documents

For more information, please view the literature below.

Spanning the Continuum of Cardiovascular Care

Specimen Requirements




1 mL

Minimum Volume

1 mL


Red-top tube or gel-barrier tube


Separate serum from cells. Transfer serum to a plastic transport tube.

Storage Instructions


Stability Requirements



Room temperature

1 day


1 day


14 days

Freeze/thaw cycles

Stable x1

Test Details


Elecsys IL-6 immunoassay is an in-vitro diagnostic test for the quantitative determination of IL-6 (interleukin-6) in human serum and plasma.1,2 This assay is used to assist in identifying severe inflammatory response in patients with confirmed COVID-19 illness to aid in determining the risk of intubation with mechanical ventilation, in conjunction with clinical findings and the results of other laboratory testing.

FDA-authorized Fact sheets for health care providers2 and patients3 can be accessed at the following links:

Fact Sheet for Health Care Providers: Elecsys IL-6–Roche Diagnostics

Fact Sheet for Patients: Elecsys IL-6–Roche Diagnostics


This test has not been FDA cleared or approved. This test has been authorized by FDA under and EUA for use by authorized laboratories.1,2 This test has been authorized only to assist in identifying severe inflammatory response, when used as an aid in determining the risk of intubation with mechanical ventilation in confirmed COVID-19 patients.1,2 This test is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of medical devices under Section 564(b)(1) of the Act, 21 U.S.C. & 360bbb-3(b),1 unless the authorization is terminated or revoked sooner.1,2

Further limitations include1,2:

• For diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination and other findings.

• Individual IL-6 levels need to be considered in combination with other clinical findings to mitigate the possible risks of false positive or false negative IL-6 results.

• In the event of a false positive result, risk to patients could include additional unnecessary intensive care admission, intubation with mechanical ventilation, and other unnecessary supportive therapy.

• Low IL-6 levels indicate that it is less likely that the patient suffers from a cytokine release syndrome and the risk for respiratory support is reduced. However, low levels if IL-6 do not preclude disease progression and future development of severe inflammatory response.

• A false negative result may occur if the test reports lower values than actual levels of IL-6 that are in the sample. When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient's clinical presentation and the presence of clinical signs and symptoms consistent with severe inflammatory response.

• Risk to a patient of a false negative result include: delayed or lack of supportive respiratory treatment, or other unintended adverse events.

• In rare cases, interference due to extremely high titers of antibodies to analyte-specific antibodies, streptavidin or ruthenium can occur. These effects are minimized by suitable test design.


Electrochemiluminescence Immunoassay (ECLIA)

Additional Information

Interleukein-6 (IL-6) is a pleiotropic cytokine that acts as both a pro-inflammatory and anti-inflammatory mediator that plays an important role in the proliferation and differentiation of cells in humans.4-7 IL-6 is involved in many physiological responses, including acute phase response, fever induction, angiogenesis, B and T cell differentiation as well as in lipid and iron metabolism.8 IL-6 is produced locally at the site of infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions.6 This essential cytokine stimulates acute phase reactions, immune responses, hematopoiesis and various internal organs to prepare for host defense.6 IL-6 is an important mediator of fever and the acute phase response that enhances the innate immune system to protect against tissue damage.7

In severe cases, IL-6 levels measured can trigger excessive defense signaling and threaten survival.9 Sustained and excessive production of IL-6 can occur in a variety of inflammatory diseases.4-7,10 Historically. the first disease to be associated with markedly elevated IL-6 was cardiac myxoma, a benign heart tumor, where increased IL-6 levels cause extensive inflammatory symptoms.11,12 Markedly elevated IL-6 levels are also found in Castleman's disease, a condition where patients suffer from severe inflammatory symptoms related to massive infiltration of mature plasma cells into lymph nodes.13 IL-6 is involved in pathogenesis of rheumatoid arthritis14,15 and other autoimmune conditions.5 Elevated levels of IL-6 in patients with community acquired pneumonia are associated with increased all-cause and cause-specific mortality during admission and over one-year post-admission, despite resolution of clinical signs of an acute infection.16-18 Increased amounts of IL-6 in serum were associated with pulmonary inflammation and extensive lung in SARS coronavirus patients.19,20

Secondary haemophagocytic lymphohistiocytosis (sHLH) is a hyperinflammatory syndrome characterized by a massive and often fatal increase in cytokine levels (including IL-6) with multi-organ failure that is most commonly triggered by viral infections.21-22 A cytokine release syndrome (CRS), similar to sHLH, with markedly increased levels of a number of cytokines including IL-6 has been reported in patients with severe COVID-19 infections.15,23-32 IL-6 levels have been found to be more elevated patients with severe COVID-19 as compared to non-severe cases26 and IL-6 has been reported to be a clinical predictor of mortality in these patients.25,28

Many patients with confirmed COVID-19 have developed fever and/or symptoms of severe inflammatory responses, sometimes referred to as "cytokine release syndrome"(CRS) or "cytokine storm."2 Severe symptoms may occur in >20% of COVID-19 patients. Symptoms of severe inflammatory response in COVID-19 may include, but are not limited to, fever, hypotension. dyspnea, organ dysfunction, and organ failure.2 Among the different cytokines that may contribute to systemic inflammation, measurement of IL-6 can be indicative of the severity of such inflammation because IL-6 is known to have a central role in inflammation.2

Measurement of IL-6 in COVID-19 confirmed patients is used to identify patients with severe inflammatory response who may be at risk of intubation with mechanical ventilation.2 Healthcare professionals may use the IL-6 measurement together with other laboratory and clinical findings. Elevated IL-6 levels may be an important indicator of severe inflammatory response.1,2 In an external study using Elecsys IL-6 on samples from 817 apparently healthy individuals, the upper limit of the reference range for IL-6 was 7 pg/mL (95th percentile).1-2

The following clinical data are from Munich, Germany, from polymerase chain reaction (PCR) confirmed symptomatic COVID patients presenting in the Emergency Department (ED). In the validation data set of 49 hospitalized patients, 19 patients required intubation for respiratory support subsequent to ED presentation.1,32 The Elecsys IL-6 assay, using a cutoff of 35 pg/mL, correctly identified 16 of the 19 patients that required intubation — positive predictive value: 59% (95% Cl = 47% to 71%); negative predictive value: 86% (95% Cl = 68% to 95%); prevalence of mechanical ventilation in COVID-19 confirmed, hospitalized patients: 39% (95% Cl = 25% to 54%).3 The cutoff was established on retrospectively collected samples (n=37) and validated with prospectively collected samples (n=49) based on the need for mechanical ventilation during the hospitalization. The receiver operator curve was calculated for the first assessment value of Elecsys IL-6 at presentation to the ED. Sensitivity and specificity is shown for patients who subsequently underwent or did not undergo intubation with mechanical ventilation.


1. Elecsys IL-6 [package instert]. Indianapolis, IN: Roche Diagnostics; 2020.
2. Fact Sheet for Health Care Providers: Elecsys IL-6–Roche Diagnostics. US Food and Drug Administration Web site. June 2, 2020. Accessed September 2020.
3. Fact Sheet for Patients: Elecsys IL-6–Roche Diagnostics. US Food and Drug Administration Web site. June 2, 2020. Accessed September 2020.
4. Uciechowski P, Dempke WCM. Interleukin-6: A Masterplayer in the Cytokine Network. Oncology. 2020;98(3):131-137.31958792
5. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014 Sep 4;6(10):a016295.25190079
6. Kishimoto T. Interleukin-6. In: Thomson AW, Lotze MT eds. Cytokine Handbook. Vol. 1, 4th ed. San Diego, CA: Academic Press; 2003:281-302.
7. Kishimoto T. IL-6: from its discovery to clinical applications. Int Immunol. 2010 May;22(5):347-352.20410258
8. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012 Feb;122(4):143-159.22029668
9. Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016 Jul;8(8):959-970.27381687
10. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015 May;16(5):448-457.25898198
11. Mendoza CE, Rosado MF, Bernal L. The role of interleukin-6 in cases of cardiac myxoma. Clinical features, immunologic abnormalities, and a possible role in recurrence. Tex Heart Inst J. 2001;28(1):3-7.11330738
12. Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B. Constitutive production of interleukin-6 and immunologic features in cardiac myxomas. Arthritis Rheum. 1990 Mar;33(3):398-402.1690543
13. Yoshizaki K, Murayama S, Ito H, Koga T. The Role of Interleukin-6 in Castleman Disease. Hematol Oncol Clin North Am. 2018 Feb;32(1):23-36.29157617
14. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012 Jul;51 Suppl 5:v3-11.22718924
15. Favalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmun Rev. 2020 May;19(5):102523.32205186
16. Tsalik EL, Jaggers LB, Glickman SW, et al. Discriminative value of inflammatory biomarkers for suspected sepsis. J Emerg Med. 2012 Jul;43(1):97-106.22056545
17. Yende S, D'Angelo G, Kellum JA, et al. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1242-1247.18369199
18. Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007 Aug 13-27;167(15):1655-1663.17698689
19. Wong CK, Lam CW, Wu AK, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004 Apr;136(1):95-103.15030519
20. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012 Mar;76(1):16-32.22390970
21. Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014 Apr 26;383(9927):1503-1516.24290661
22. Seguin A, Galicier L, Boutboul D, Lemiale V, Azoulay E. Pulmonary Involvement in Patients With Hemophagocytic Lymphohistiocytosis. Chest. 2016 May;149(5):1294-1301.26836913
23. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513.32007143
24. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034.32192578
25. McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Apr 3:102537.32251717
26. Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768.32161940
27. Wan S, Yi Q, Fan S, et al. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol. 2020 May;189(3):428-437.32297671
28. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062.32171076
29. Mandel M, Harari G, Gurevich M, Achiron A. Cytokine prediction of mortality in COVID19 patients. Cytokine. 2020 Oct;134:155190.32673995
30. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020 Jun 6;395(10239):1763-1770.32442528
31. Liu F, Li L, Xu M, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020 Jun;127:104370.32344321
32. Herold T, Jurinovic V, Arnreich C, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4.32425269


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140916 Interleukin-6, Serum 26881-3 140922 Interleukin-6, Serum pg/mL 26881-3

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