Circulating Interleukin-37 Levels in Healthy Adult Humans – Establishing a Reference Range

Santarelli, Danielle M.; Vincent, Fabien B.; Rudloff, Ina; Nold-Petry, Claudia A.; Nold, Marcel F.; Russo, Marc

doi:10.3389/fimmu.2021.708425

Cited by 7 publications

(7 citation statements)

References 85 publications

(104 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the available data, it was not possible to define a reliable refence range for IL-38 in healthy volunteers, as was possible for the IL-37 data extracted from literature ( 13 ). This is remarkable as IL-37 has several isoforms that will probably not be determined by all ELISA kits ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating interleukin-38 concentrations in healthy adults

Teufel

Graaf²,

Netea³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Interleukin (IL)-38 is the latest discovered member of the interleukin-1 family, which has anti-inflammatory properties similar to IL-36Ra. Several studies compared circulating IL-38 concentrations in healthy and diseased populations to characterize its role in both auto-immune and inflammatory pathologies, with both higher and lower concentrations being associated with certain diseases. However, in order to use IL-38 as a biomarker, a reference range in healthy adults is needed. To establish a reference IL-38 circulating concentration, accessible data from 25 eligible studies with IL-38 concentrations in healthy adults was collected. To validate the values found in literature, we measured IL-38 concentrations by enzyme-linked immunosorbent assay (ELISA) in several cohorts from our own institute. Additionally, the effect of blood collection techniques, freeze thawing cycles, and hemolysis on IL-38 measurements was assessed. To evaluate the importance of the genetic background of individuals as confounding factor of IL-38 synthesis, we used publicly available eQTL databases with matched data on allele frequencies in individuals of different ethnicities. Mean IL-38 concentrations in the various studies were weighted by their corresponding sample size, resulting in a weighted mean, and weighted upper and lower limits were calculated by mean ± 2 SD. Differences of over 10.000-fold were found in the weighted means between studies, which could not be attributed to the blood collection method or assessment of IL-38 in plasma or serum. Although IL-38 concentrations were markedly higher in Chinese then in European population studies, we could not show an association with the genetic background. From our analysis, a reference range for circulating IL-38 in healthy adults could thus not yet be established.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In 2013, a comprehensive overview of several cytokine and chemokine concentrations in 72 healthy adults was published, however, also here IL-38 was not part of study ( 12 ). Recently, a similar study established a reference range of IL-37 circulating concentrations in healthy adults based on studies from literature ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating interleukin-38 concentrations in healthy adults

Teufel

Graaf²,

Netea³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…In most participants, however, these values were at low levels, ranging from 3.40 to 38.00 pg/mL. According to the available evidence, these range values belong to the lower reference range for healthy adults [ 33 ]. There was a gentle rise in the 3rd, compared to the 2nd quartile, and a steep uprise in the upper quartile, so the distribution curve acquired the non-linear “J” shape.…”

Section: Discussionmentioning

confidence: 99%

“…Before the clinical utility of IL-37 becomes possible in cardio-metabolic conditions, there is a need to establish the reference range for this cytokine in healthy adults and patient subgroups [ 33 ]. The problem with these conditions is that they are characterized by high complexity, as already shown for patients with T2D.…”

Section: Introductionmentioning

confidence: 99%

A Critical Appraisal of the Diagnostic and Prognostic Utility of the Anti-Inflammatory Marker IL-37 in a Clinical Setting: A Case Study of Patients with Diabetes Type 2

Bosnić

Babič

Anderková

et al. 2023

IJERPH

View full text Add to dashboard Cite

Background: The role of the cytokine interleukin-37 (IL-37) has been recognized in reversing inflammation-mediated metabolic costs. The aim was to evaluate the clinical utility of this cytokine as a diagnostic and prognostic marker in patients with type 2 diabetes (T2D). Methods: We included 170 older (median: 66 years) individuals with T2D (females: 95) and classified as primary care attenders to assess the association of factors that describe patients with plasma IL-37 levels (expressed as quartiles) using multinomial regression models. We determined the diagnostic ability of IL-37 cut-offs to identify diabetes-related complications or patient subgroups by using Receiver Operating Characteristic analysis (c-statistics). Results: Frailty status was shown to have a suppressive effect on IL-37 circulating levels and a major modifying effect on associations of metabolic and inflammatory factors with IL-37, including the effects of treatments. Situations in which IL-37 reached a clinically significant discriminating ability included the model of IL-37 and C-Reactive Protein in differentiating among diabetic patients with low–normal/high BMI ((<25/≥25 kg/m2), and the model of IL-37 and Thyroid Stimulating Hormone in discriminating between women with/without metabolic syndrome. Conclusions: The study has revealed limitations in using classical approaches in determining the diagnostic and prognostic utility of the cytokine IL-37 in patients with T2D and lain a foundation for new methodology approaches.

show abstract

“…Although the AdipoGen ELISA has been widely used in human studies to assess circulating IL-37 concentrations in various disease states [ 16 , 18 , 52 , 67 , 69 ], there has been concern in the field regarding its validity and specificity [ 52 ]. Using multiple approaches, we systematically established, for the first time in an independent setting, that the assay is accurate, reproducible, and specific to IL-37 (i.e., it did not detect IL-1ra, a cytokine with very similar structural and chemical homology).…”

Section: Discussionmentioning

confidence: 99%

Circulating interleukin-37 declines with aging in healthy humans: relations to healthspan indicators and IL37 gene SNPs

et al. 2022

View full text Add to dashboard Cite

Aging is characterized by declines in physiological function that increase risk of age-associated diseases and limit healthspan, mediated in part by chronic low-grade inflammation. Interleukin (IL)-37 suppresses inflammation in pathophysiological states but has not been studied in the context of aging in otherwise healthy humans. Thus, we investigated associations between IL-37 and markers of healthspan in 271 young (18–39 years; n = 41), middle-aged (40–64 years; n = 162), and older (65 + years; n = 68) adults free of overt clinical disease. After conducting a thorough validation of AdipoGen’s IL-37 ELISA, we found that plasma IL-37 is lower in older adults (young: 339 ± 240, middle-aged: 345 ± 234; older: 258 ± 175 pg/mL; P = 0.048), despite elevations in pro-inflammatory markers. As such, the ratios of circulating IL-37 to pro-inflammatory markers were considerably lower in older adults (e.g., IL-37 to C-reactive protein: young, 888 ± 918 vs. older, 337 ± 293; P = 0.02), indicating impaired IL-37 responsiveness to a pro-inflammatory state with aging and consistent with the notion of immunosenescence. These ratios were related to multiple indicators of healthspan, including positively to cardiorespiratory fitness ( P < 0.01) and negatively to markers of adiposity, blood pressure, and blood glucose (all P < 0.05). Lastly, we correlated single-nucleotide polymorphisms (SNPs) in the IL37 and ILR8 (the co-receptor for IL-37) genes and found that variants in IL37 SNPs tended to be associated with blood pressure and adiposity ( P = 0.08–0.09) but did not explain inter-individual variability in circulating IL-37 concentrations across age ( P ≥ 0.23). Overall, our findings provide novel insights into a possible role of IL-37 in biological aging in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-022-00587-3.

show abstract

Circulating Interleukin-37 Levels in Healthy Adult Humans – Establishing a Reference Range

Cited by 7 publications

References 85 publications

Circulating interleukin-38 concentrations in healthy adults

Circulating interleukin-38 concentrations in healthy adults

A Critical Appraisal of the Diagnostic and Prognostic Utility of the Anti-Inflammatory Marker IL-37 in a Clinical Setting: A Case Study of Patients with Diabetes Type 2

Circulating interleukin-37 declines with aging in healthy humans: relations to healthspan indicators and IL37 gene SNPs

Contact Info

Product

Resources

About