Interleukin-2, Plasma

CPT: 83520
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Synonyms

  • IL-2
  • IL2

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-2 (IL-2) 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).

The cytokine Interleukin-2 (IL-2) exerts crucial functions during immune homeostasis via its effects on regulatory T (Treg) cells, and the optimizing and fine-tuning of effector lymphocyte responses.4 IL-2 acts as a growth factor for T cells and serves as a key component of immune activation.5-7 Somewhat paradoxically, gene knockout mouse studies have provided evidence that the primary IL-2 function in vivo is the suppression of T responses. Mice lacking IL-2 or its receptor develop lymphadenopathy and T cell-mediated autoimmunity.5,8 Interleukin-2 receptor (IL-2R) signaling regulates tolerance and immunity with deficient signaling resulting in autoimmunity.5,9 The therapeutic action of IL-2 is related to concentration. Low doses of recombinant IL-2 have been used for Treg cell-based immunosuppressive strategies against immune pathologies, while high-dose IL-2 has shown some success in stimulating antitumor immune responses.4,5

The cellular receptor for IL-2 is a three-chain molecule.5 The receptors signaling function is mediated by the beta and gamma chains, which are expressed on T cells (and natural killer cells) constitutively, can be up-regulated by activation and dimerize to bind IL-2 with low affinity.5 The alpha chain of the IL-2 receptor (CD25) has no signaling capacity but confers on the receptor the ability to bind IL-2 with high-affinity.5 T cell activation induces IL-2 production and upregulates the high-affinity IL-2 receptor subunit CD25, increasing T-cell responsiveness to IL-2.5,9 Binding of IL-2 to its high-affinity receptor causes T cells to proliferate about 1,000-fold in the secondary lymphoid organs, producing a large population of lymphoblasts, also termed effector cells.10 IL-2 binding to its receptor stimulates increased cytokine synthesis and potentiates Fas-mediated apoptosis. It causes proliferation and activation of NK cells and B-cell proliferation and antibody synthesis. Also, it stimulates the activation of cytotoxic lymphocytes and macrophages.11 IL-2R signaling influences two discrete aspects of immune responses by CD8(+) T cells, terminal differentiation of effector cells in primary responses and aspects of memory recall responses.9

IL-2 is produced mainly by CD4b helper T cells 5 and a subset of CD8 cells.12 T cells that express high levels of CD25 are essential for maintaining self-tolerance. A class of T cells, known as regulatory T cells (Tregs), are defined by the co-expression of CD25 and the transcription factor forkhead box P3 (FOXP3).5,9 Studies indicate that IL-2 not only stimulates immune responses and generates effector cells but also is required for Treg-mediated suppression of immune responses.5 A major and essential function of IL-2 is to maintain self tolerance and prevent autoimmunity, and depletion or decreased production of this cytokine is associated with systemic autoimmunity.5

Although exposure of a memory CD8 cells to their cognate antigen generally induces reactivation and cytotoxicity, sustained antigen exposure during chronic infection and cancer can cause exhaustion.13 Exhausted CD8 T-cells lose effector function, fail to self-renew and have defective memory responses. They are characterized by high expression of inhibitory receptors, expression of specific transcriptional regulators and metabolic dysfunction. While T cell exhaustion is undesirable in the setting of infection and malignancy, it can protect from autoimmunity. Both soluble and cellular mediators can regulate exhaustion in CD81 T-cells. IL-10 can induce exhaustion, whereas IL-2 can promote or repress exhaustion depending on the timing and duration of exposure.12

A meta-analysis found that elevated IL-2 was strongly associated with acute respiratory distress syndrome mortality.14


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):e200443334114369
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. Arenas-Ramirez N, Woytschak J, Boyman O. Interleukin-2: Biology, Design and Application. Trends Immunol. 2015 Dec;36(12):763-777.26572555
5. Abbas AK. The Surprising Story of IL-2: From Experimental Models to Clinical Application. Am J Pathol. 2020 Sep;190(9):1776-1781.32828360
6. Roediger B, Kyle R, Tay SS, et al. IL-2 is a critical regulator of group 2 innate lymphoidcell function during pulmonary inflammation. J Allergy Clin Immunol. 2015 Dec;136(6):1653-1663.e7.26025126
7. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995 Aug 1;155(3):1151-1164.7636184
8. Justiz Vaillant AA, Qurie A. Interleukin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.2022 Aug 22.29763015
9. Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between toleranceand immunity. Immunity. 2010 Aug 27;33(2):153-165.20732639
10. 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
11. Bachmann MF, Oxenius A. Interleukin 2: from immunostimulation to immunoregulation and back again. EMBO Rep. 2007 Dec;8(12):1142-1148.32217835
12. Kahan SM, Bakshi RK, Ingram JT, et al. Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection. Sci Immunol. 2022 Feb 11;7(68):eabl632235148200
13. McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T cell exhaustion during chronic viral infection and cancer. Annu Rev Immunol. 2019 Apr 26;37:457-495.30676822
14. Terpstra ML, Aman J, van Nieuw Amerongen GP, Groeneveld AB. Plasma biomarkers for acute respiratory distress syndrome: a systematic review and meta-analysis*. Crit Care Med. 2014 Mar;42(3):691-700.24158164

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140812 Interleukin-2, Plasma 33939-0 140813 Interleukin-2, Plasma pg/mL 33939-0

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