Effects of early life stress on brain cytokines: A systematic review and meta-analysis of rodent studies

Exposure to early life stress (ELS) may lead to long-lasting neurobiological and behavioral impairments. Alterations in the immune system and neuroinflammatory state induced by ELS exposure are considered risk factors for developing psychiatric disorders. Here, we performed a systematic review and meta-analysis of rodent studies investigating the short and long-term effects of ELS exposure on anti and pro-inflammatory cytokines in brain tissues. Our analysis shows that animals exposed to ELS present an increase in pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha. On the other hand, no alteration was observed in the anti-inflammatory cytokine IL-10. Metaregression revealed that alterations were more prominent in the hippocampus of adult animals that were exposed to more extended periods of ELS. These inflammatory effects were not permanent since few alterations were identified in aged animals. Our findings suggest that ELS exposure alters pro-inflammatory cytokines expression and may act as a primer for a secondary challenge that may induce lifelong immune alterations. Moreover, the actual evidence is insufficient to comprehend the relationship between anti-inflammatory cytokines and ELS fully.