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 12,421 values for IL-6 in the blood of healthy adult 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% confidence interval [CI]: 4.631, 5.740). As the age increased by 1 year, IL-6 values increased by 0.05 pg/ml (95% CI: 0.02, 0.09; p < .01). Though the heterogenicity, as determined by I² 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, for example, COVID-19.