Effects of interferon-?, interleukin-1?, and tumor necrosis factor-? on the serotonin metabolism in the nucleus raphe dorsalis of the rat

Abstract

The effects of the cytokines interferon (IFN)-gamma, interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha on the serotoninergic transmission in the nucleus raphe dorsalis (NRD) were studied after peripheral and central application. The studies were performed in the freely moving rat using differential pulse voltammetry with multicarbon fibre electrodes to study the extracellular levels of the serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA). The extracellular 5-HIAA levels were not changed in the NRD after peripheral application of rat recombinant IFN-gamma, but elevated by the cytokines IL-1 beta and TNF-alpha. After intracerebroventricular (i.c.v.) application the cytokines IFN-gamma, IL-1 beta and TNF-alpha stimulated the serotoninergic transmission in the NRD. Our data suggest that the effect of peripherally elevated cytokine concentrations on the serotonin metabolism in the NRD of the rat is cytokine-dependent. In this respect the T-cell and NK-cell cytokine IFN-gamma acts clearly different when compared to the mainly macrophage-derived cytokines IL-1 beta and TNF-alpha, and plays a different role in the communication between immune and central nervous system.

Major Depression and Activation of The Inflammatory Response System

“…Peripherally and central administration of IL-lp, IFNy, and TNFa increase extracellular 5-HT concentrations in several brain areas such as the hypothalamus, the hippocampus, and the cortex (Clement, Buschmann, Rex, Grote, Opper, Gemsa, & Wesemann, 1997). IL-ip modulates the activity of the 5-HT transporter (Ramamoorthy, Ramamoorthy, Prasad, Bhat, Mahesh, Leibach, & Ganapathy, 1995), which plays a central role in serotonergic neurotransmision by reuptake of 5-HT.…”

Mechanisms of Cancer-Related Fatigue

“…There is evidence that proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, can influence 5-HT metabolism. Evidence suggests the existence of a feedback loop between TNF-α and central 5-HT [52] in which peripherally synthesized TNF-α causes an increase in 5-HT release into the synaptic space [53]. In addition, TNF-α can increase 5-HT transporter function, resulting in increased clearance of 5-HT from the synaptic space [54,55].…”

Effects of Antidepressants on Weight and on the Plasma Levels of Leptin, TNF-α and Soluble TNF Receptors A Longitudinal Study in Patients Treated with Amitriptyline or Paroxetine

“…Alternatively, the increase in sTNFR-p75 plasma levels could be part of a cascade of reactions initiated by the drugs, and the observed alteration of the TNF-␣ system would then be the consequence of effects on the metabolic system. Both options allow for additional involvement of central and peripheral neurotransmitters such as serotonin, adrenalin, noradrenalin, and histamine which were shown to be linked with the TNF-␣ system (Chou et al 1996;Clement et al 1997;Kawashima et al 1998; for review see Müller and Ackenheil 1998).…”