Defining IL-6 Levels in Healthy Individuals: A Meta-Analysis

BACKGROUND: Interleukin-6 (IL-6) is produced by and impacts different cell types in human IL-6 is associated with different diseases and viral infections including COVID-19 To our knowledge no normal values were reported for IL-6 in the blood of healthy individuals We have reviewed and performed a meta-analysis on a total of 140 studies including 12421 values for IL-6 in the blood of adult healthy donors Among these studies 83 did not report a mean value and the standard deviation Therefore, for the statistical analysis we used the values reported in 57 studies which included 3166 values for IL-6 RESULTS: The reported values for IL-6 in the blood of healthy donors varied between 0 and 43 5 pg/ml The pooled estimate of IL-6 was 5 186 pg/ml (95% CI: 4 631, 5 740) As the age increased by one year, IL-6 values increased by 0 05 pg/ml (95% CI: 0 02, 0 09;p<0 01) Though the heterogenicity as determined by I(2) statistics was high in our study, the differences in IL-6 values are still at the level of a few pg/ml, which might be related to the differences in the conditions that influence IL-6 production in the healthy population CONCLUSIONS: This is the first meta-analysis reporting the levels of IL-6 in the blood of healthy donors based on a large number of studies and donors Therefore the 95% CI values determined in our study could well serve as a reference range for quick decision making in clinical interventions particularly those aiming to inhibit IL-6 especially urgent interventions e g COVID-19 This article is protected by copyright All rights reserved