Circulating interleukin-38 concentrations in healthy adults

Abstract

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.

Exploratory analysis of interleukin‐38 in hospitalized COVID‐19 patients

“…However, we recently demonstrated that the blood collection method does not influence the IL-38 concentrations detected by enzyme-linked immunosorbent assay (ELISA). 55 We further observed a positive correlation between Ddimer and IL-38 in men of the validation cohort. Elevated D-dimer is a prognostic marker for severe COVID-19, 56 as well as for thrombotic complications, and is associated with increased proinflammatory cytokine levels such as IL-6.…”

“…A potential confounder for the detection of IL‐38 may be due to differences between plasma and serum. However, we recently demonstrated that the blood collection method does not influence the IL‐38 concentrations detected by enzyme‐linked immunosorbent assay (ELISA) 55 …”

“…However, we recently demonstrated that the blood collection method does not influence the IL‐38 concentrations detected by enzyme‐linked immunosorbent assay (ELISA). 55 …”

Interleukin-38 Level and Polymorphism (Rs 6743376) Associated with Rheumatoid Arthritis

“…Analyzing IL-38 and rs6743376 in the context Rheumatoid Arthritis (RA) is crucial for several reasons (Teufel et al, 2022). Firstly, understanding IL-38's role offers potential therapeutic avenues by regulating inflammatory responses in RA.…”