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IL-1Ra (Interleukin 1 Receptor Antagonist)

Analyte: Interleukin-1 soluble receptor antagonist

Specimen Type: Serum

Optimum Volume: 1.0 mL

Stability:

2-8°C -20°C -70°C
3 d 6 mo 1.4 y

Reporting units: pg/mL

Method: ELISA

Biological or Clinical Significance:

Interleukin-1 receptor antagonist (IL-1ra; also known as IL-1F3) is a 22 – 25 kDa member of the IL-1 family of cytokines.  IL-1ra is a pure cytokine receptor antagonist that has no signal transduction-initiating activity.  It is an acute phase protein that exists to dampen inflammation.  IL-1 (β) is initially produced by monocytes in response to a variety of stimuli.  Circulating IL-1 then binds to widely expressed IL-1 type I receptors (IL-1 RI) and initiates a number of pro-inflammatory events.  On endothelial cells (EC), IL-1 induces PGE2 and IL-6 release, generating fever, thrombocytosis, and hepatic acute phase protein production.  In synovial joints, IL-1 induces chondrocyte nitric oxide production, an event that leads to reduced collagen synthesis and chondrocyte apoptosis.  Finally, IL-1 increase neutrophil counts, both in blood and tissue, and thus is able to promote a pro-inflammatory environment in multiple locations.  IL-1ra blocks IL-1 action through competitive inhibition.  More correctly, although IL-1ra fills the IL-1 binding site in IL-1 RI, it is also unable to orchestrate the creation of a signal-transducing IL-1 RI:IL-1R Accessory protein (IL-1 R AcP) heterodimer complex.  Effective IL-1ra concentrations are generally 100-fold greater than local IL-1 concentrations.  This is because the IL-1ra half-life is but 6 min, and very few IL-1 type I receptors need to be engaged by IL-1 to elicit a cellular response.

Principle of Test Method:

The Quantikine® Human IL-1ra Immunoassay is a 4.5 h solid phase ELISA designed to measure IL-1ra in cell culture supernates, serum, and plasma.  It contains E. coli-derived recombinant human IL-1ra as well as antibodies raised against the recombinant factor.  This assay employs the quantitative sandwich enzyme immunoassay technique.  A monoclonal antibody specific for IL-1ra has been pre-coated onto a microplate.  Standards and samples are pipetted into the wells and any IL-1ra present is bound by the immobilized antibody.  After washing away any unbound substances, an enzyme-linked polyclonal antibody specific for IL-1ra is added to the wells.  Following a wash to remove any unbound antibody-enzyme reagent, a substrate solution is added to the wells and color develops in proportion to the amount of IL-1ra bound in the initial step.  The color development is stopped and the intensity of the color is measured at a wavelength of 450 nm with a correction wavelength at 544 nm.

References:

1. Danis VA, Millington M, Hyland VJ, Grennan D. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol 1995; 99:303-310.
2. Willis C, Morris JM, Danis V, Gallery EDM. Cytokine production by peripheral blood monocytes during the normal human ovulatory menstrual cycle. Human Reprod 2003; 18:1173-1178.
3. Lekander M, Elofsson S, Neve IM, Hansson LO, Unden AL. Self-rated health is related to levels of circulating cytokines. Psycho Med 2004; 66:559-563.

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