After rigorous activity tests IL-1F7 was officially designated IL-37 (3). IL-37 mRNA has been detected in various hematopoietic organs as well as in other tissues (1).
IL-37 is strongly expressed intracellularly in human monocytes where expression can be further upregulated by LPS (4). IL-37 was shown to bind to the IL-18R without eliciting signal transduction (5). A demonstration of IL-37's immunological capability was shown by Th1-dependent anti-tumor immunity induced by intratumoral expression of IL-37 (6).
Upon LPS stimulation the NH2-terminal prodomain of IL-37 encompassing 1st-45th amino acid residues is cleaved by caspase-1 and the resulting mature IL-37 actively translocates into the nucleus, where it suppresses the induction of TNF-α, IL-6, and MIP-2. Interaction of Smad3 with the translocated IL-37 has been an acting mechanism for the IL-37-mediated anti-inflammation (3), suggesting that IL-37 is a potent inhibitor of innate immunity. Measurement of intracellular IL-37 upon danger signals or proinflammatory cues would provide a novel insight into anti-inflammation.
Sandwich type ELISA
Interleukin-37, Interleukin-1 family member 7 (IL-1F7), Interleukin-1 homolog 4 (IL-1H4), Interleukin-1 zeta, Interleukin-1-related protein (IL-1RP1), IL-23
Principle of Method
This assay is a sandwich Enzyme Linked-Immunosorbent Assay (ELISA) for quantitative determination of human IL-37 in biological fluids. A polyclonal antibody specific for IL-37 has been precoated onto the 96-well microtiter plate. Standards and samples are pipetted into the wells for binding to the coated antibody. After extensive washing to remove unbound compounds, IL-37 is recognized by the addition of a polyclonal antibody specific for IL-37 (Detection Antibody). After removal of excess polyclonal antibody, HRP conjugated anti-rabbit IgG (HRP) is added. Following a final washing, peroxidase activity is quantified using the substrate 3,3’,5,5’-tetramethylbenzidine (TMB). The intensity of the color reaction is measured at 450 nm after acidification and is directly proportional to the concentration of IL-37 in the samples.
Serum and Plasma : 50 µL (actual amount of sample loaded in well after dilution).
Calibration Range: 0.016 ng/ml – 1 ng/ml
Limit of Detection
Intra-assay (Within-Run) C.V.
Inter-assay (Run-to-Run) C.V.
References to Summary
- Four new members expand the interleukin-1 superfamily: D.E. Smith, et al.; J. Biol. 275, 1169 (2000)
- A Complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity: P. Bufler, et al.; PNAS 99, 13723 (2002)
- IL-37 is a fundamental inhibitor of innate immunity: M.F. Nold, et al.; Nat. Immunol. 11, 1014 (2010)
- Interleukin-1 homologues IL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharide: P. Bufler, et al.; Biochem. J. 381, 503 (2004)
- Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-gamma production: S. Kumar, et al.; Cytokine 18, 61 (2002)
- Innate immunity mediated by the cytokine IL-1 homologue 4 (IL-1H4/IL-1F7) induces IL-12-dependent adaptive and profound antitumor immunity: W. Gao, et al.; J. Immunol. 170, 107 (2003)