Fluoxetine and Desipramine Inhibit Dendritic Cell-mediated Host Inflammatory Immune Responses

Objective: Recent studies reported that antidepressant drugs may possess anti-inflammatory effects. Therefore, in the context of periodontal disease, this study investigated the effects of both Fluoxetine (FLU), a selective serotonin reuptake inhibitor, and Desipramine (DES), a tricyclic antidepressant, on the host inflammatory responses mediated by dendritic cells (DCs). Methods: To establish primary culture of DCs, bone marrow cells from C57BL/6 wild type mice were cultured with GM-CSF (20 ng/mL) for 6 days, and the differentiated DCs were isolated using MACS beads (CD11c-positive selection). DCs (20,000 cells/well) were then incubated with or without LPS (1 μg/mL) in the presence or absence of FLU or DES (0.01, 0.1 or 1 μM) for 24 hours in RPMI medium. The harvested culture supernatants were subjected to ELISA to measure the concentrations of cytokines and chemokines produced by DCs in response to LPS, including IL-1β, IL-12, TNF-α, RANTES (CCL5) and MIP-1α (CCL3). Statistical analysis was performed using ANOVA, followed by Bonferroni's post hoc test, and values of p<0.05 were considered statistically significant. Results: Both FLU and DES suppressed the production of IL-1β and IL-12 from LPS-stimulated DCs (p<0.05), whereas FLU and DES had no statistically significant effects on the LPS-mediated increase of TNF-α production (p>0.05). The production of RANTES and MIP-1α by LPS-stimulated DC was also down-regulated by FLU and DES (p<0.05). The viability of DCs was not affected by neither FLU nor DES at all concentrations tested, as monitored by MTT assay. Conclusion: This study demonstrated that Fluoxetine and Desipramine could inhibit the production of pro-inflammatory cytokines and chemokines by DCs, while not affecting the viability of DCs. These data clearly suggested that some classes of antidepressant agents may lead to the development of a novel class of anti-inflammatory treatment for periodontal disease. (NIH grants DE-18499 and DE-019917; PDEE/CAPES-BEX 4073/08-8 and FAPESP #2008/00566-6, Brazil).