Amitriptyline and nortriptyline inhibit interleukin-1β and tumour necrosis factor-α release by rat mixed glial and microglial cell cultures

Abstract

Pro-inflammatory cytokines, such as interleukin (IL)-1β and tumour necrosis factor (TNF)-α have been suggested to be involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs. Until now the effect of antidepressants on cytokines has been examined only in plasma, blood mononuclear cells and spleen, which reflect the activity of peripheral cytokine network. The aim of this study was to evaluate the effect of amitriptyline and its metabolite nortriptyline on the release of IL-1β and TNF-α by lipopolysaccharide (LPS)-activated rat mixed glial and microglial cell cultures. LPS stimulated the release of both cytokines. The exposure of mixed glial culture to amitriptyline and nortriptyline led to a decrease in both IL-1β and TNF-α release. Moreover, amitriptyline reduced LPS-stimulated IL-1β release by microglial cultures. Although amitriptyline reduced secretion of both cytokines, the drug did not affect IL-1β and TNF-α mRNAs in mixed cell cultures. Our study has shown for the first time that amitriptyline and nortriptyline administered at concentrations which may be achieved in plasma and brain structures during treatment, inhibit the secretion of IL-1β and TNF-α in rat mixed glial and microglial cell cultures. The obtained results support the previous observations that antidepressants are able to reduce peripheral release of pro-inflammatory cytokines and suggest that the cytokine network may be involved in the central mechanism of action of amitriptyline and nortriptyline. Copyright © 2005 CINP.