Abstract

Elevated levels of pro-inflammatory biomarkers have been reported in major depressive disorder (MDD). The aim of this study is to investigate the plasma levels of interleukin-18 (IL-18), macrophage-inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein 1 (MCP-1), stromal cell derived factor-1 (SDF-1), and regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with MDD before and after eight week treatment of fluoxetine hydrochloride in comparison with normal controls. All subjects were assessed before and after treatment with the Hamilton Depression Rating Scale (HDRS). Our results showed that the symptoms of forty healthy controls and thirty-four patients with MDD were correlated with their plasma levels of IL-18, MIP-1α, MCP-1, SDF-1α, and RANTES. The levels of all five cytokine of patients with MDD were significantly decreased after treatment. However, the levels remained significantly higher than those of the healthy controls (p<0.001). In the seven depressed subjects whose HDRS score fell to below seven after antidepressant therapy comparing with those subjects whose HDRS score larger than seven, the mean levels of IL-18 (p=0.01) and SDF-1α(p<0.05) were significantly lower. Conversely, higher levels of cytokines correlated with a persistently increased severity of symptoms, as measured by the HDRS scores. In conclusion, these findings suggest that MDD is associated with activation of the immune system, and the antidepressant effect of fluoxetine may be mediated in part through its anti-inflammatory effects.

Key words: Fluoxetine hydrochloride, major depression, cytokine, chemokine, inflammation.

Abbreviation

MDD, Major depressive disorder; HPA, hypothalamic-pituitary-adrenal; MCP-1, monocyte chemoattractant protein 1; SDF-1, stromal cell derived factor-1; MIP-1α, macrophage-inflammatory protein-1α; RANTES, regulated upon activation, normal T cell expressed and secreted; 5-HT, 5-hydroxytryptamine; IL-6,interleukin-6; SSRI,  Selective serotonin reuptake inhibitors; HDRS, Hamilton depression rating scale; ESR, erythrocyte sedimentation rates; ELISA, enzyme-linked immunosorbant assay; TNF, tumor necrosis factor; TRP, tryptophan; LTP,long-term potentiation;  NMDA, N-methyl d-aspartate.