EFFECTS OF INTERFERON-GAMMA, INTERLEUKIN-1-BETA, AND TUMOR-NECROSIS-FACTOR-ALPHA ON THE SEROTONIN METABOLISM IN THE NUCLEUS RAPHE DORSALIS OF THE RAT

The effects of the cytokines interferon (IFN)-gamma, interleukin (IL)- 1, and tumor necrosis factor (TNF)-alpha on the serotoninergic transmi ssion in the nucleus raphe dorsalis (NRD) were studied after periphera l and central application. The studies were performed in the freely mo ving rat using differential pulse voltammetry with multicarbon fibre e lectrodes to study the extracellular levels of the serotonin (5-HT) me tabolite 5-hydroxyindoleacetic acid (5-HIAA). The extracellular 5-HIAA levels were not changed in the NRD after peripheral application of ra t recombinant IFN-gamma, but elevated by the cytokines IL-1 beta and T NF-alpha. After intracerebroventricular (i.c.v.) application the cytok ines IFN-gamma, IL-1 beta and TNF-alpha stimulated the serotoninergic transmission in the NRD. Our data suggest that the effect of periphera lly elevated cytokine concentrations on the serotonin metabolism in th e 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 th e mainly macrophage-derived cytokines IL-1 beta and TNF-alpha, and pla ys a different role in the communication between immune and central ne rvous system.