TNF alpha reduces glutamate induced intracellular Ca2+ increase in cultured cortical astrocytes

The proinflammatory cytokine TNF alpha is locally released during various i nflammatory CNS diseases and high cerebrospinal fluid (CSF) titers of TNF a lpha were found in meningitis patients. We know from previous studies that TNF alpha also depolarizes astrocytes by reducing their inwardly rectifying K+ currents. We have now investigated the effect of TNF alpha on the gluta mate induced intracellular Ca2+ increase in astrocytes, a process which see ms to be involved in glial mediated modulation of neuronal synaptic transmi sssion. Incubation with TNF alpha (50-1000 U/ml for 60 min) reduces the glu tamate induced intracellular Ca2+ increase in astrocytes but not in neurons and this seems to be a phenomenon secondary to the TNF alpha induced depol arization. While other proinflammatory cytokines (interleukin 1 beta, IL-2, IL-6) did not interfere with the astrocytic glutamate response, incubation in CSF from septic meningitis patients (CSF-SM) also reduced the glutamate induced intracellular Ca2+ increase. The application of a neutralizing ant i-TNF alpha antibody to the CSF-SM prior to cell incubation partially resto red the glutamate response. Our data suggest that inflammatory molecules su ch as TNF alpha impair astrocytes' response to glutamate and this may indir ectly affect neuronal synaptic transmission. (C) 2001 Elsevier Science B.V. All rights reserved.