Local immune regulation in the central nervous system by substance P vs. glutamate

The response of parenchymal microglia to interferon-gamma (IFN-gamma) varie s across the brain. To ask if local neurochemicals contribute to site-speci fic control, the influence of substance P (SP) and glutamate was evaluated in brainstem vs. hippocampus. In brainstem, stereotaxic injection of SP inc reased class II MHC upregulation by IFN-gamma, while a SP receptor antagoni st (Spantide I) prevented it. In hippocampus, where the baseline response t o IFN-gamma was lower, SP was ineffective, but blocking glutamate enhanced the response in a proportion of rats. Attempts to understand and control im mune activity in the CNS should take the local neurochemical environment in to account. (C) 2001 Elsevier Science B.V. All rights reserved.