Interleukin-8, Serum

CPT: 83520
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Synonyms

  • IL-8
  • IL8

Expected Turnaround Time

4 - 7 days



Related Documents


Specimen Requirements


Specimen

Serum


Volume

0.5 mL


Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)


Container

Red-top tube or gel-barrier tube


Collection

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


Storage Instructions

Refrigerate; stable for seven days. Stable at room temperature for three days. Stable frozen for 14 days. Freeze/thaw cycles x2.


Causes for Rejection

Gross hemolysis; gross lipemia


Test Details


Use

This test is used for the measurement of Interleukin-8 (IL-8) levels in serum.


Limitations

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

Enzyme-linked immunosorbent assay (ELISA)


Additional Information

Cytokines are low-molecular-weight intercellular signaling molecules that are produced de novo in response to an immune stimulus.1-3 They regulate immune cell homeostasis by mediating innate and acquired immunity and inflammation in human health and disease. They generally (although not always) act over short distances and short time spans and at very low concentrations. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior. Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation and secretion of effector molecules. It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types (pleiotropy). Cytokines are redundant in their activity, meaning similar functions can be stimulated by different cytokines. Cytokines are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines can also act synergistically (two or more cytokines acting together) or antagonistically (cytokines causing opposing activities).

Interleukin-8 (IL-8) is a potent neutrophil-specific chemotactic factor that is an important mediator of the immune reaction in the innate immune system response. In 2002, IL-8 was assigned the name CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies.4 Its primary receptors were similarly renamed; (IL8 receptor, alpha to CXCR1 and IL8 receptor, beta to CXCR2). IL-8 is expressed in various cell types including neutrophils, fibroblasts, epithelial cells, hepatocytes, alveolar macrophages, airway smooth muscle cells and endothelial cells.5-7 Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies.8,9 Increased IL-8 concentrations have been found in inflammatory sites in patients with diseases such as psoriasis, rheumatoid arthritis, respiratory syncytial virus infection, asthma and chronic obstructive pulmonary diseases.10

IL-8 mediates its biological effects through the binding to CXC chemokine receptors, CXCR1 and CXCR2, which activates a phosphorylation cascade to trigger chemotaxis and neutrophil activation as part of the inflammatory response.11,12 It induces chemotaxis in target cells, primarily neutrophils, causing them to migrate toward the site of infection.13 While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (endothelial cells, macrophages, mast cells and keratinocytes) that respond to this chemokine. IL-8 also stimulates phagocytosis once neutrophils arrived at the site of infection. IL-8 is also known to be a potent promoter of angiogenesis.14 Another key function of the cell signaling stimulated by CXCL8 is the initiation of the oxidative burst. This process allows the buildup of proteolytic enzymes and reactive oxygen species (ROS) that are necessary to break down the epithelial basement membrane. The release of ROS and damaging enzymes is regulated to minimize host damage while carrying out it effector functions.13

Dysregulated signaling by IL-8 has been implicated as a possible cause of Acute Respiratory Distress Syndrome (ARDS).15-17 Patients with pancreatitis who developed ARDS have demonstrated significantly higher serum concentrations of IL-8 expression (indicative of neutrophil activation) compared to patients without ARDS.18 Elevated levels of IL-8 have also been reported in patients with transfusion-related acute lung injury (TRALI).19

The recent world-wide pandemic of Coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a dramatic increase in patients with acute respiratory failure and ARDS, both of which are associated with increased mortality, healthcare cost and post-recovery morbidity.12 Neutrophil activation caused by IL-8 has been implicated in the pathogenesis and progression of this disease. In patients with severe COVID-19, IL-8 is one of the main chemokines responsible for recruitment, activation and accumulation of neutrophils. Increased IL-8 levels has been associated with the development of acute kidney injury, a complication of COVID-19, and respiratory failure as shown by a reduction in PaO2/FiO2.20 IL-8 has demonstrated to be significantly higher in nonsurvivors compared to survivors of COVID-19, and the dynamic change of the serum IL-8 levels has been correlated with the severity of the disease.21-24 IL-8 serum levels have also been shown to correlate better than IL-6 levels with overall clinical disease scores.22,25 Elevated serum levels of IL-8 have been associated with longer duration of illness in patients with severe or critical COVID-19.26 IL-8 has been associated with the recruitment and activation of polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC) that inhibit the response by T-cells to SARS-CoV-2.27 Additionally, the frequency of PMN-MDSCs in critical COVID-19 patients is higher in non-survivors compared with survivors, and the frequency of PMN-MDSCs is positively correlated with plasma levels of IL-8 in hospitalized COVID patients.27

IL-8 has been shown to have multiple pro-tumorigenic roles within the tumor microenvironment, including stimulating proliferation or transformation of tumor cells into a migratory or mesenchymal phenotype.28-30 Further, IL-8 can increase tumor angiogenesis or recruit larger numbers of immunosuppressive cells to the tumor.28 In several malignancies, patients with higher levels of IL-8 at baseline experience worse clinical outcomes.28,31-35 Additionally, studies have shown that the chemokine directly contributes to the development of resistance to both chemotherapy and molecularly targeted agents.28 More recently, clinical studies evaluating levels of IL-8 in patients receiving immune checkpoint inhibition (ICI) therapy deduced that myeloid tumor infiltration driven by IL-8 contributes to resistance to ICI agents and that peripheral IL-8 can predict outcomes to ICI therapy.28


Footnotes

1. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: from clinical significance to quantification. Adv Sci (Weinh). 2021 Aug;8(15):e2004433.34114369
2. Chopp L, Redmond C, O'Shea JJ, Schwartz DM. From thymus to tissues and tumors: A review of T-cell biology. J Allergy Clin Immunol. 2023 Jan;151(1):81-97. Epub 2022 Oct 19.36272581
3. Akdis M, Aab A, Altunbulakli C, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016 Oct;138(4):984-1010.27577879
4. Bacon K, Baggiolini M, Broxmeyer H, et al. Chemokine/chemokine receptor nomenclature. J Interferon Cytokine Res. 2002 Oct;22(10):1067-1068.12433287
5. Hedges JC, Singer CA, Gerthoffer WT. Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes. Am J Respir Cell Mol Biol. 2000 Jul;23(1):86-94.10873157
6. Coelho AL, Hogaboam CM, Kunkel SL. Chemokines provide the sustained inflammatory bridge between innate and acquired immunity. Cytokine Growth Factor Rev. 2005 Dec;16(6):553-560.15967703
7. Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. Int J Inflam. 2011;2011:908468.22235381
8. Wolff B, Burns AR, Middleton J, Rot A. Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies. J Exp Med. 1998 Nov 2;188(9):1757-1762.9802987
9. Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells. J Exp Med. 1998 Nov 2;188(9):1751-1756.9802986
10. Beigelman A, Isaacson-Schmid M, Sajol G, et al. Randomized trial to evaluate azithromycin's effects on serum and upper airway IL-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis. J Allergy ClinImmunol. 2015 May;135(5):1171-1178.e1.25458910
11. Akdis M, Palomares O, van de Veen W, van Splunter M, Akdis CA. TH17 and TH22 cells: a confusion of antimicrobial response with tissue inflammation versus protection. J Allergy Clin Immunol. 2012 Jun;129(6):1438-1449.22657405
12. Cesta MC, Zippoli M, Marsiglia C, et al. The role of interleukin-8 in lung inflammation and injury: implications for the management of COVID-19 and hyperinflammatory acute respiratory distress syndrome. Front Pharmacol. 2022 Jan 12;12:808797.35095519
13. Dixit N, Simon SI. Chemokines, selectins and intracellular calcium flux: temporal and spatial cues for leukocyte arrest. Front Immunol. 2012 Jul 10;3:188.22787461
14. Pekalski ML, García AR, Ferreira RC, et al. Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2. JCI Insight. 2017 Aug 17;2(16):e93739.28814669
15. Fremont RD, Koyama T, Calfee CS, et al. Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis. J Trauma. 2010 May;68(5):1121-1127.20038857
16. Ha H, Debnath B, Neamati N. Role of the CXCL8-CXCR1/2 axis in cancer and inflammatory diseases. Theranostics. 2017 Apr 7;7(6):1543-1588.28529637
17. Kaiser R, Leunig A, Pekayvaz K, et al. Self-sustaining IL-8 loops drive a prothrombotic neutrophil phenotype in severe COVID-19. JCI Insight. 2021 Sep 22;6(18):e150862.34403366
18. Browne GW, Pitchumoni CS. Pathophysiology of pulmonary complications of acute pancreatitis. World J Gastroenterol. 2006 Nov 28;12(44):7087-7096.17131469
19. Roubinian NH, Looney MR, Kor DJ, et al. Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions. Transfusion. 2015 Aug;55(8):1838-1846.25702590
20. Bülow Anderberg S, Luther T, Berglund M, et al. Increased levels of plasmacytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients. Cytokine. 2021 Feb;138:155389.33348065
21. Chen L, Wang G, Tan J, et al. Scoring cytokine storm by the levels of MCP-3 and IL-8 accurately distinguished COVID-19 patients with high mortality. Signal Transduct Target Ther. 2020 Dec 14;5(1):292.33318472
22. Nagant C, Ponthieux F, Smet J, et al. A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer. Int J Infect Dis. 2020 Dec;101:342-345.33039609
23. Li J, Rong L, Cui R, Feng J, et al. Dynamic changes in serum IL-6, IL-8, and IL-10 predict the outcome of ICU patients with severe COVID-19. Ann Palliat Med. 2021;10(4):3706-3714.33615814
24. Del Valle DM, Kim-Schulze S, Huang HH, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020 Oct;26(10):1636-1643.32839624
25. Li L, Li J, Gao M, et al. Interleukin-8 as a biomarker for disease prognosis of coronavirus disease-2019 Patients. Front Immunol. 2021 Jan 8;11:602395.33488599
26. Ma A, Zhang L, Ye X, et al. High Levels of Circulating IL-8 and Soluble IL-2R Are Associated With Prolonged Illness in Patients With Severe COVID-19. Front Immunol. 2021 Jan 29;12:626235.33584733
27. Sacchi A, Grassi G, Bordoni V, et al. Early expansion of myeloid-derived suppressorcells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19outcome. Cell Death Dis. 2020 Oct 27;11(10):921.33110074
28. Fousek K, Horn LA, Palena C. Interleukin-8: A chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression. Pharmacol Ther. 2021 Mar;219:107692.32980444
29. David JM, Dominguez C, Hamilton DH, Palena C. The IL-8/IL-8R axis: a double agent in tumor immune resistance. Vaccines (Basel). 2016 Jun 24;4(3):22.27348007
30. Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res. 2008 Nov 1;14(21):6735-6741.18980965
31. Chen SJ, Lian GD, Li JJ, et al. Tumor-driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL-8. Cancer Med. 2018 Nov;7(11):5679-5690.30311406
32. Feng L, Qi Q, Wang P, et al. Serum levels of IL-6, IL-8, and IL-10 are indicators of prognosis in pancreatic cancer. J Int Med Res. 2018 Dec;46(12):5228-5236.30304975
33. Sanguinete MMM, Oliveira PH, Martins-Filho A et al. Serum IL-6 and IL-8 Correlate with Prognostic Factors in Ovarian Cancer. Immunol Invest. 2017 Oct;46(7):677-688.28872976
34. Keskin S, Kutluk AC, Tas F. Prognostic and predictive role of angiogenic markers in non-small cell lung cancer. Asian Pac J Cancer Prev. 2019 Mar 26;20(3):733-736.30909672
35. Tiainen L, Hämäläinen M, Luukkaala T, et al. Low plasma IL-8 levels during chemotherapy are predictive of excellent long-term survival in metastatic breast cancer. Clin Breast Cancer. 2019 Aug;19(4):e522-e533.31029558

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140918 Interleukin-8, Serum 33211-4 140919 Interleukin-8, Serum pg/mL 33211-4

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