37. The effect of antidepressants, polyunsaturated fatty acids and glucocorticoid pre-treatment on inflammation in human hippocampal stem cells

Evidence suggests that the efficacy of conventional antidepressants and fish oil in depression may be due to their anti-inflammatory properties. We set out to investigate these properties in a relevant model of depression - human hippocampal stem cells inflamed by addition of Il-1beta. Furthermore, we aimed to explore the apparent paradox presented by the co-existence of high levels of inflammation and glucocorticoids in depressed populations (given that glucocorticoids are potently anti-inflammatory) using a glucocorticoid pre-treatment paradigm. Venlafaxine (1 uM) and EPA (10uM) both decreased the amount of IL-6 in the supernatant of the cells (measured by ELISA) upon co-treatment with IL-1beta - by 16% (p < 0.05) and 11.3% (p < 0.01), respectively. However, DHA and sertraline increased the amount of IL-6 detected upon co-treatment with IL-1beta - by 18% (p < 0.01) and 8% (p < 0.05), respectively. The anti-inflammatory effect of venlafaxine appeared to be at least partially transcriptional: there were trends towards decrease in IL-6 gene expression (11%) and NF-kB DNA binding (7.3%). The anti-inflammatory effect of EPA was also matched by a decrease in NFKB binding activity (15%, p < 0.001).Paradoxically, the increase in IL-6 produced by sertraline was associated with a decrease in NF-kB binding (11.5%, p < 0.001).Finally, pre-treatment with dexamethasone potentiated subsequent inflammatory responses, in a dose- and time-dependent manner with the greatest potentiation (38%, p < 0.01) occurring at a dexamethasone dose of 100nM with a pre-treatment interval of 24 h.