Aberrations in peripheral blood interleukin-6 levels in post-traumatic stress disorder: A systematic review and meta-analysis.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a complex psychiatric condition that occurs in individuals after experiencing or witnessing a terrifying event. Although numerous studies have explored the relationship between immune activation and PTSD, the results regarding the association between PTSD and interleukin-6 (IL-6) remain inconsistent. OBJECTIVE: The purpose of this study is to clarify the association between peripheral blood IL-6 and PTSD, as well as to explore the potential factors that may affect this association. METHOD: We conducted a comprehensive literature search using PubMed, Embase, Web of Science, Cochrane library and PsycINFO databases. A fixed- or random-effects model was used to calculate the pooled effect size (Hedges' g). Sensitivity analysis, publication bias, Galbraith plot and subgroup analysis were carried out using Comprehensive Meta-Analysis software version 3.0 (CMA 3.0) and Stata/MP software. RESULTS: A total of 1738 manuscripts were screened for initial eligibility, and 43 studies reported in 36 articles met the inclusion criteria were included in the meta-analysis. The primary analysis revealed moderate effects (Hedges' g = 0.493, 95 % CI: 0.275-0.710, p < 0.001) of peripheral blood IL-6 levels in PTSD patients compared to healthy controls. Sensitivity analysis confirmed the robustness of our findings. Additionally, the association between peripheral blood IL-6 and PTSD remained unchanged even after excluding studies outside the Galbraith plot. Despite the presence of publication bias, the association between IL-6 and PTSD persisted after correction using the trim-and-fill method. Subgroup analysis yielded similar results, except the non-traumatic control subgroup and the female subgroup, highlighting the important role of IL-6 in pathophysiological processes within individuals with PTSD. CONCLUSIONS: In our study, the present results showed that elevated peripheral blood IL-6 levels may be associated with PTSD. More clinical studies with larger sample size are required in the future.