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Evaluation of patients with suspected systemic infection; evaluation of patients with suspected chronicinflammatory disorders.
Results of this test are for research purposes only by the assay's manufacturer. The performance characteristics of this assay have not been established. Results should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.
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.1-4 IL-6 plays an important role in many physiological responses, such as acute phase response, fever induction, angiogenesis, B and T cell differentiation and lipid and iron metabolism.5 IL-6 is produced locally from 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.3 This essential cytokine transmits defense signals from a pathogen invasion or tissue damage site to stimulate acute phase reactions, immune responses, hematopoiesis and various internal organs to prepare for host defense.3 IL-6 is an important mediator of fever and the acute phase response that enhances the innate immune system and protects against tissue damage.4 In severe cases, IL-6 levels measured can trigger excessive defense signaling and threaten survival.6
Sustained and excessive production of IL-6 is associated with various inflammatory diseases.1-3,7 The first clinical condition associated with markedly elevated IL-6 was cardiac myxoma, a benign heart tumor, where increased IL-6 levels cause extensive inflammatory symptoms.8,9 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.10 IL-6 is both elevated and involved in pathogenesis of rheumatoid arthritis11,12 and other autoimmune conditions.2 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.13-15 Increased amounts of IL-6 in serum were associated with pulmonary inflammation and extensive lung damage in SARS coronavirus patients.16,17
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.18-19 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.12,20-25 IL-6 levels have been found to be more elevated patients with severe COVID-19 as compared to non-severe cases23 and IL-6 has been reported to be a clinical predictor of mortality in these patients.22,25
1. Uciechowski P, Dempke WCM. Interleukin-6: A Masterplayer in the Cytokine Network. Oncology. 2020;98(3):131-137. PubMed 31958792
2. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014 Sep 4;6(10):a016295. PubMed 25190079
3. Kishimoto T. Interleukin-6. In: Thomson AW, Lotze MT eds. Cytokine Handbook. Vol. 1, 4th ed. San Diego, CA: Academic Press; 2003:281-302.
4. Kishimoto T. IL-6: from its discovery to clinical applications. Int Immunol. 2010 May;22(5):347-352. PubMed 20410258
5. 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. PubMed 22029668
6. Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016 Jul;8(8):959-970. PubMed 27381687
7. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015 May;16(5):448-457. PubMed 25898198
8. 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. PubMed 11330738
9. 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. PubMed 1690543
10. 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. PubMed 29157617
11. Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012 Jul;51 Suppl 5:v3-11. PubMed 22718924
12. 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. PubMed 32205186
13. 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. PubMed 22056545
14. 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. PubMed 18369199
15. 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. PubMed 17698689
16. 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. PubMed 15030519
17. 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. PubMed 22390970
18. Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014 Apr 26;383(9927):1503-1516. PubMed 24290661
19. Seguin A, Galicier L, Boutboul D, Lemiale V, Azoulay E. Pulmonary Involvement in Patients With Hemophagocytic Lymphohistiocytosis. Chest. 2016 May;149(5):1294-1301. PubMed 26836913
20. 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. PubMed 32007143
21. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. PubMed 32192578
22. 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. PubMed 32251717
23. Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020 Mar 12. pii: ciaa248. [Epub ahead of print] PubMed 32161940
24. 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):4
