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

Said, Elias A; Al-Reesi, Iman; Al-Shizawi, Nawal; Jaju, Sanjay; Al-Balushi, Mohammed S; Koh, Crystal Y; Al-Jabri, Ali A; Jeyaseelan, Lakshmanan

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 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 e.g. COVID-19. This article is protected by copyright. All rights reserved.