Major depression accompanied with inflammation and multiple cytokines alterations: Evidences from clinical patients to macaca fascicularis and LPS-induced depressive mice model

Inflammation progress has been consistently implicated in the pathophysiology of major depressive disorder (MDD). However, the underlying mechanism of inflammation and depressive symptoms still far from being fully elucidated. In addition, studies on emotional disorders could also benefit from model of the non-human primates. To explore the difference of serum multi-cytokines levels among the MDD patients and depressed macaca fascicularis as well as LPS-treated mice, thus may find the reliable potential biomarkers for MDD. Serum multi-cytokines levels among MDD patients (n = 44) and depressed macaca fascicularis (n = 6) together with controls (n = 22 for human, n = 6 for macaques) were detected by the Bio-Plex cytokines panel. Then five of these serum cytokines in LPS-treated mice were measured via ELISA. Furthermore, these cytokines protein expressions were validated by western blotting in three depression-related regions of LPS-treated mice. Here, we found that MDD patients displayed increased concentration of 13 proinflammatory and anti-inflammatory cytokines accompanied with one decreased cytokine in peripheral serum. Meanwhile, the naturally occurring depression (NOD) macaca fascicularis merely exhibited elevated concentration of 4 peripheral cytokines (IL-6, IL-8, MCP-1, VEGF), which were in accordance with the outcomes of MDD patients. Importantly, the serum and brain tissues of LPS-treated mice also emerged similar cytokines alterations. In summary, our findings strengthen the evidence that cytokines were associated with the depression, and the IL-6 and VEGF may as predictive biomarkers for novel diagnostic as well as therapeutic of depression. The hypothalamus may as a key brain region involve in the inflammatory related depressive-like behaviors.