Revisiting bupropion anti-inflammatory action: involvement of the TLR2/TLR4 and JAK2/STAT3

AbstractThere are accumulating reports regarding poor response to common antidepressant therapy. Antidepressant resistance is often linked to inflammatory system activation and patients displaying inflammation prior to the treatment are less responsive to antidepressants. We hypothesized that the inefficacy of antidepressant therapy in some patients may be attributable to the drugs ’ inflammatory mode of action, which has been overlooked because of their substantial therapeutic benefit. Bupropion is a commonly prescribed antidepressant that is often used to treat seasonal affective disorders as well. Nevertheless, research suggests that bupropion causes inflammation and wors ens depressive symptoms. Therefore, we investigated the impact of bupropion on cytokines of innate and adaptive immunity, as well as immune signaling pathways. We treated lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) with different doses of bupropion. Pro-/anti -inflammatory cytokines [tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1β), IL-17, and IL-10] were assessed at both transcriptional and translational levels as well as the involvement of JAK2 /STAT3, TLR2, and TLR4 signaling in this process. Bupropion reduced IL-17A, TNFα, and IL-1β pr otein levels in the cultures. Nonetheless, bupropion increased IL-1β (P <  0.0001), TNFα (P <  0.0001), and IL-17A (P <  0.05) mRNA levels. Treatment enhanced both IL-10 concentration (P ...
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research