Paroxetine treatment markedly ameliorates the clinical symptoms of collagen-induced arthritis (CIA) in rats, effectively preventing joint histological damage and reducing T cell infiltration into the synovium. It also strongly inhibits the production of CX3CL1 in synovial tissues^[1].

Administered at 20 mg/kg/day, Paroxetine decreases the cross-sectional area of myocytes and reduces reactive oxygen species (ROS) formation in the remote myocardium of rats. This treatment reduces the risk of ventricular tachycardia and diminishes left ventricular remodeling and arrhythmia susceptibility post-myocardial infarction (MI), likely through its effects on ROS levels^[2].

Paroxetine, at concentrations of 1 μM and 10 μM, significantly inhibits T cell migration induced by CX3CL1 by blocking GRK2 activity. This inhibition also extends to GRK2-mediated activation of the ERK signaling pathway^[1].

At a concentration of 10 μM, Paroxetine decreases the levels of pro-inflammatory cytokines in LPS-stimulated BV2 microglial cells. Furthermore, Paroxetine (0-5 μM) shows a dose-dependent reduction in the LPS-induced production of TNF-α and IL-1β in these cells. It also curbs the LPS-induced production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in BV2 cells. At 5 μM, Paroxetine inhibits LPS-induced JNK activation and reduces baseline ERK1/2 activity, contributing to its ability to mitigate microglial-mediated neurotoxicity and suppress pro-inflammatory cytokines and NO production in primary microglial cells^[4].