Interleukin-10, Plasma

CPT: 83520
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Synonyms

  • IL-10
  • IL10

Expected Turnaround Time

4 - 7 days



Related Documents


Specimen Requirements


Specimen

Plasma


Volume

0.5 mL


Minimum Volume

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


Container

Lavender-top (EDTA) tube


Collection

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


Storage Instructions

Refrigerate; stable for 14 days. Stable at room temperature or frozen for 14 days. Freeze/thaw cycles x3.


Causes for Rejection

Gross hemolysis; gross lipemia


Test Details


Use

This test is used for the measurement of Interleukin-10 (IL-10) levels in plasma.


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).

IL-10 is an anti-inflammatory cytokine that inhibits the activity of a number of cells involved in pathogen clearance including TH1 cells, NK cells and macrophages.3-7 Secretion of IL-10 can directly limit effector T cell responses, and it can also indirectly suppress T cell responses by limiting the antigen presenting capacity of antigen presenting cells.8,9 IL-10 inhibits the expression of many proinflammatory cytokines, chemokines and chemokine receptors.3 It causes inhibition of IL-2 and interferon gamma. It decreases the antigen presentation and MHC class II expression of dendritic cells and co-stimulatory molecules on macrophages, and it also downregulates pathogenic TH17 cell responses. It inhibits IL-12 production by macrophages.5 In contrast to its inhibitory effects on T cells, IL-10 promotes the survival, proliferation and differentiation of human B cells and increases IgG4 production.3 IL-10 causes inhibition of IL-2 and interferon gamma. A number of different types of cells can produce IL-10 including monocytes, T cells (mainly type 1 Treg cells),8 B cells (mainly Breg cells), a small fraction of NK cells, macrophages and dendritic cells. The predominant source of IL-10 varies in different tissues and can differ in acute or chronic stages of the infection.5,6

IL-10 plays a significant role in immune suppression in allergen immunotherapy.3,10,11 This cytokine is thought to mediate allergen tolerance in allergen immunotherapy and in individuals with exposure to high doses of allergens, such as beekeepers and cat owners.12,13 Elevated serum IL-10 levels have been associated with lower subsequent risks of worsening asthma control and attacks in adults.14,15 Elevated levels of IL-10 have been observed in the blood of patients with chronic spontaneous urticaria (CSU) compared with healthy controls.16 Subgroup analyses has revealed higher levels of IL-10 in acute versus chronic urticaria.16 Higher levels of IL-10 have been observed in autologous serum skin test (ASST) positive versus ASST–negative CSU.16 In subjects with systemic mastocytosis, the number of mast cells is elevated many fold.3,17 Mast cells produce IL-10 add peak levels in patients with severe mast cell activation events can be elevated as much as seven-fold above baseline.18,19 IL-10 has been associated with various events in rheumatoid arthritis, such as hyperplasia of synoviocytes, inflammatory cell infiltration and bone tissue destruction.20 IL-10 also plays a role in bone metabolic diseases and in fracture healing by regulating osteogenesis.20 IL-10 has been shown to regulate the growth of the giant cell tumor of the bone (GCTB) and osteosarcoma.20

IL-10 elevation is a common finding in patients with hyperinflammation syndromes.21-23 Hyperinflammation is a life-threatening pathologic state associated with a constellation of clinical disorders, including haemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome, severe coronavirus disease 2019 (COVID-19), sepsis and cytokine release syndrome.21-23 Although these disease entities have differential etiological factors, they share a significant number of clinical symptoms, such as fever, hepatosplenomegaly, hepatitis, cytopenia, hyperferritinemia and multiorgan failure. The collection of these manifestations is also described as cytokine storm syndrome.23 Recent studies suggest inflammatory cell death–mediated cytokine release is crucial in mediating the inflammation and tissue damage in this syndrome.21

Studies have shown that serum levels of IL-10 in patients with severe COVID-19 infection with cytokine storm can be markedly elevated.24-26 A longitudinal study of COVID-19 infection found that an elevation of IL-10 is an early event—one preceding the elevations of other cytokine storm-associated proinflammatory cytokines.25 It has also been shown that COVID-19 patients admitted to the intensive care unit (ICU) have significantly elevated serum levels of IL-10 relative other non-ICU COVID-19 patients.24,27 A meta-analysis of results from a number of studies found that IL-10 can be an effective criterion for discerning the severity and predicting the course of the disease in patients with COVID-19.28 Several studies suggest that the production and increase of IL-10 during COVID-19 can play a detrimental pathological role, especially during hyperinflammatory periods.29

IL-10 has historically be classified as an anti-inflammatory cytokine with immunosuppressive effects.21 As a result, the marked elevation of IL-10 during hyperinflammation has long been interpreted as a protective mechanism to dampen the over-activated proinflammatory reactions and prevent damage to the host.21 However, recent studies suggest that a high IL-10 level may also be an unfavorable prognostic factor in both HLH29,30 and severe COVID-19.25,31 These lines of evidence, along with findings supporting proinflammatory activities of IL-10, have led to speculation that IL-10 may play a pathologic role in hyperinflammatory conditions.29,32


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. Justiz Vaillant AA, Qurie A. Interleukin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2022 Aug 22.29763015
5. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180(9):5771-5777.18424693
6. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765.11244051
7. Oral HB, Kotenko SV, Yilmaz M, et al. Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26. Eur J Immunol. 2006 Feb;36(2):380-388.16365913
8. Freeborn RA, Strubbe S, Roncarolo MG. Type 1 regulatory T cell-mediated tolerance in health and disease. Front Immunol. 2022 Oct 28;13:1032575.36389662
9. de Waal-Malefyt R, Haanen J, Spits H, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human t cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915-924.1655948
10. Stanic B, van de Veen W, Wirz OF, et al. IL-10-overexpressing B cells regulate innate and adaptive immune responses. J Allergy Clin Immunol. 2015 Mar;135(3):771-780.e8.25240783
11. van de Veen W, Stanic B, Yaman G, et al. IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013 Apr;131(4):1204-1212.23453135
12. Meiler F, Zumkehr J, Klunker S, Rückert B, Akdis CA, Adkis M. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J Exp Med. 2008 Nov 24;205(12):2887-2898.19001136
13. Akdis CA, Akdis M. Mechanisms of immune tolerance to allergens: role of IL-10 and Tregs. J Clin Invest. 2014 Nov;124(11):4678-4680.25365074
14. Akiki Z, Rava M, Diaz Gil O, et al. Serum cytokine profiles as predictors of asthma control in adults from the EGEA study. Respir Med. 2017 Apr;125:57-64.28340863
15. Figueiredo CA, Barreto ML, Alcantara-Neves NM, et al. Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil. J Allergy Clin Immunol. 2013 Jun;131(6):1683-1690.23273955
16. Chen Q, Zhong H, Chen WC, et al. Different expression patterns of plasma Th1-, Th2-, Th17- and Th22-related cytokines correlate with serum autoreactivity and allergen sensitivity in chronic spontaneous urticaria. J Eur AcadDermatol Venereol. 2018 Mar;32(3):441-448.28846158
17. Valent P, Akin C, Bonadonna P, et al. Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome. J Allergy Clin Immunol Pract. 2019 Apr;7(4):1125-1133.e1.30737190
18. Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol Rev. 2018 Mar;282(1):121-150.29431212
19. Boehm T, Ristl R, Mühlbacher J, Valent P, Wahrmann M, Jilma B. Massive release of TH2 cytokines induced a cytokine storm during a severe mast cell activation event in a patient with indolent systemic mastocytosis. J Allergy Clin Immunol. 2022 Aug;150(2):406-414.35504498
20. Ni S, Shan F, Geng J. Interleukin-10 family members: Biology and role in the bone and joint diseases. Int Immunopharmacol. 2022 Jul;108:108881.35623292
21. Tang Y, Xu Q, Luo H, et al. Excessive IL-10 and IL-18 trigger hemophagocytic lymphohistiocytosis-like hyperinflammation and enhanced myelopoiesis. J Allergy Clin Immunol. 2022 Nov;150(5):1154-1167.35792218
22. Weaver LK, Behrens EM. Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and haemophagocytic lymphohistiocytosis. Curr Opin Rheumatol. 2014 Sep;26(5):562-569.25022357
23. Karki R, Kanneganti TD. The ‘‘cytokine storm’’: molecular mechanisms and therapeutic prospects. Trends Immunol. 2021 Aug;42(8):681-705.34217595
24. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506.31986264
25. Zhao Y, Qin L, Zhang P, et al. Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease. JCI Insight. 2020 Jul 9;5(13):e139834.32501293
26. Wang F, Hou H, Luo Y, et al. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight. 2020 May 21;5(10):e137799.32324595
27. Diao B, Wang C, Tan Y, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 2020 May 1;11:827.32425950
28. Dhar SK, K V, Damodar S, Gujar S, Das M. IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression. Heliyon. 2021 Feb;7(2):e06155.33553782
29. Tang Y, Xu X, Song H, et al. Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome. Br J Haematol. 2008 Oct;143(1):84-91.18673367
30. Zhou Y, Kong F, Wang S, et al. Increased levels of serum interleukin-10 are associated with poor outcome in adult hemophagocytic lymphohistiocytosis patients. Orphanet J Rare Dis. 2021 Aug 4;16(1):347.34348761
31. Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020 Dec;9(1):1123-1130.32475230
32. Islam H, Chamberlain TC, Mui AL, Little JP. Elevated interleukin-10 levels in COVID-19: potentiation of pro-inflammatory responses or impaired antiinflammatory action? Front Immunol. 2021 Jun 21;12:677008.34234779

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140820 Interleukin-10, Plasma 26848-2 140821 Interleukin-10, Plasma pg/mL 26848-2

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