Fluvoxamine inhibits some inflammatory genes expression in LPS/stimulated human endothelial cells, U937 macrophages, and carrageenan-induced paw edema in rat

Abstract

Objective(s): Fluvoxamine is a well-known selective serotonin reuptake inhibitor (SSRI); Despite its antiinflammatory effect, little is known about the precise mechanisms involved. In our previous work, we found that IP administration of fluvoxamine produced a noticeable anti-inflammatory effect in carrageenan-induced paw edema in rats. In this study, we aimed to evaluate the effect of fluvoxamine on the expression of some inflammatory genes like intercellular adhesion molecule (ICAM(1)), vascular cell adhesion molecule (VCAM(1)), cyclooxygenases(2) (COX2), and inducible nitric oxide synthase (iNOS). Materials and Methods: An in vitro model of LPS stimulated human endothelial cells and U937 macrophages were used. Cells were pretreated with various concentrations of fluvoxamine, from 10(-8) M to 10(-6) M. For in vivo model, fluvoxamine was administered IP at doses of 25 and 50 mg/kg(-1), before injection of carrageenan. At the end of experiment, the expression of mentioned genes were measured by quantitative real time (RT)-PCR in cells and in paw edema in rat. Results: The expression of ICAM(1), VCAM(1), COX2, and iNOS was significantly decreased by fluvoxamine in endothelial cells, macrophages, and in rat carrageenan-induced paw edema. Our finding also confirmed that IP injection of fluvoxamine inhibits carrageenan-induced inflammation in rat paw edema. Conclusion: The results of present study provide further evidence for the anti-inflammatory effect of fluvoxamine. This effect appears to be mediated by down regulation of inflammatory genes. Further studies are needed to evaluate the complex cellular and molecular mechanisms of immunomodulatory effect of fluvoxamine.