Noradrenergic control of inflammatory processes in the central nervous system

Abstract

Evidence suggests tliat the monoannine neurotransmitter noradrenaline (NA) elicits anti-inflammatory actions in the central nervous system (CNS), and consequently may play an endogenous neuroprotective role in CNS disorders where inflammatory events contribute to pathology. In line with this hypothesis, we demonstrate that in vitro exposure of primary cortical mixed glial cells to NA suppresses expression of the pro-inflammatory cytokines IL-1β and TNF-α, suppresses induction of iNOS and nitric oxide production, and also suppresses mRNA expression of the chemokines RANTES, IP-10 and MIP-1α in response to the inflammagen lipopolysaccharide (LPS). Interestingly, NA also decreased production of the anti-inflammatory cytokine IL-10, but failed to alter production of the related anti-inflammatory cytokine TGF-β. As previous studies indicate that the noradrenaline reuptake inhibitor (NRI) desipramine (DMI) has anti-inflammatory properties, we examined the ability of DMI, and also the highly selective NRI atomoxetine (ATX), to alter pro-inflammatory cytokine production in mixed glial cells. In addition, as glial cells carry the noradrenaline transporter we hypothesized that NRIs may increase the anti¬inflammatory actions of NA by inhibiting its reuptake from the culture medium.