Defining IL‐6 levels in healthy individuals: A meta‐analysis

Abstract 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 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, for example, COVID‐19.