Alterations of pro- and anti-inflammatory cytokines balance and superoxide dismutase in the dorsolateral prefrontal cortex of suicide decedents.

Recent studies have suggested that the immune system may be a key player in the pathophysiology of suicide. In this context, access to brain samples from individuals who died by suicide is of particular importance. Our study is designed to thoroughly investigate the link between suicide and brain immune system alterations. We analyzed changes in gene and protein expression of proinflammatory cytokines, IL-6 and TGF-β, and anti-inflammatory cytokine, IL-10, in the dorsolateral prefrontal cortex (DLPFC) of 33 suicide decedents (S) (with no clinical psychiatric history or treatment with anxiolytics or antidepressants) and 29 controls (C) using qPCR and ELISAs, respectively. Additionally, we evaluated superoxide dismutase 1 (SOD1) activity using ELISAs. S and C were matched for age and postmortem interval. Our results revealed an inverse correlation between pro- and anti-inflammatory cytokine levels in the DLPFC of S compared to C, with IL-6 and TGF-β increased and IL-10 reduced. Interestingly, contrasting changes were noted in gene expression across all analyzed targets, suggesting a potential homeostatic compensatory mechanism that warrants further analysis in large-scale studies. These alterations were accompanied by lower SOD1 activity in the DLPFC of S compared to C. These findings indicate an association between an inflammatory brain state and increased oxidative stress with suicide.