Depression is a common mental disease with disastrous effect on the health and wealth globally. Focusing on the role for
inflammation and immune activation in the pathogenesis of depression, many tries have been taken into effect targeting at the blockage of inflammatory
cytokines, among which
interleukin- 6 (IL-6) and its receptor antagonist
tocilizumab attracts more attention, with inconsistent findings. Moderate to severe
depressive disorder (MSDD) patients were enrolled and the serum concentrations of
IL-6 and
tumor necrosis factor-α (TNF-α) measured, their correlation with the Hamilton Depression Rating Scale-24 (HAMD-24) scores was analyzed, and their role in discriminating MSDD patients from the health controls were evaluated. Meanwhile, a depression rat model was established by
intraperitoneal injection of LPS, and
tocilizumab was administrated doing 50 mg/kg via
intravenous injection. The behavioral performance was observed, the serum concentration of
IL-6, TNF-α, and
C-reactive protein (CRP) was measured, and the
protein expression of
IL-6 and TNF-α in the hippocampus were also detected. The activity of the Hypothalamic-pituitary-adrenal (HPA) axis was observed, and the
protein expression levels in the hippocampus were detected via western blot. Moreover, the immunofluorescence staining (IF) technique was used to investigate the co-location of
IL-6 and neuron (MAP2), astrocyte (GFAP), or microglial (IBA-1). The results showed that the serum
IL-6 level was significantly increased in the MSDD patients and
lipopolysaccharide (LPS)-challenged rats, with a significant correlation with the HAMD-24 scores or struggling time in the FST and
corticosterone (CORT) abundance. Results of ROC analysis showed a significant diagnosis value of
IL-6 in discriminating MSDD patients or depression rats from the controls in the present study.
Tocilizumab could relieve the depression-like behaviors induced by LPS, together with a normal abundance of serum CORT and hypothalamic CRH expression. Moreover,
tocilizumab could alleviate the "inflammatory storm" and impaired hippocampal synaptic plasticity in LPS-challenged depression rats, inhibiting the hyperactivation of astrocyte and microglia, decreasing the peripheral and central abundance of
IL-6, CRP, and TNF-α, and balancing the hippocampal expression levels of synaptic plasticity-associated
proteins and key molecular in Wnt/β-
catenin signaling pathway. These results indicated a predictive role of
IL-6 in discriminating depression from controls, and demonstrated an
antidepressant effect of
tocilizumab in LPS-challenged rats, targeting at the inflammatory storm and the subsequent impairments of hippocampal synaptic plasticity.