Interleukin-6 Levels in Serum, Plasma, and Cerebral Spinal Fluid in Individuals with Suicide Behavior: Systematic Review and Meta-Analysis with Meta-Regression

Evidence suggests that interleukin-6 (IL-6) concentrations have an important role in suicide behavior (SB) as they are usually increased in these individuals, although no conclusive outcomes have been attained. The purpose of this study was to evaluate the IL-6 levels in plasma, serum, and cerebral spinal fluid (CSF) to determine through a meta-analysis if these levels are increased in individuals with SB in comparison to a group. We calculated the standardized mean difference and 95% confidence intervals (95% CIs). In the systematic review, 21 studies were included, while in the meta-analysis, we included nine studies. The results of our meta-analysis indicated that individuals with SB had reduced levels of IL-6 in plasma (d - 0.189, 95% CI: -0.274 to -0.103, Z, P (Q) = 0.339, I2= 7.478), but increased levels of IL-6 in serum (d - 1.14, 95% CI: 0.658 to 1.630, Z, P (Q) = 0.26, I2= 7.47) and CSF (d 0.64, 95% CI: 0.245 to 1.035, Z, P (Q) = 0.163, I2= 44.80). The meta-regression analysis showed an association between males and high IL-6 levels in plasma (P = 0.003) and serum (P = 0.010), but not the central nervous system (CNS), while age was not associated with IL-6 levels in any of the samples evaluated (plasma, serum, or CNS). The present meta-analysis indicates that serum and CNS IL-6 levels are increased in individuals with SB, while plasma IL-6 levels are decreased, highlighting the importance of the biological sample at the moment of selecting IL-6 as biomarker. However, we need more studies performed in different populations that measure IL-6 and also consider gender when these measures are performed.