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

The response of parenchymal microglia to interferon-gamma (IFN-gamma) varies across the brain. To ask if local neurochemicals contribute to site-specific control, the influence of substance P (SP) and glutamate was evaluated in brainstem vs. hippocampus. In brainstem, stereotaxic injection of SP increased class II MHC upregulation by IFN-gamma, while a SP receptor antagonist (Spantide I) prevented it. In hippocampus, where the baseline response to IFN-gamma was lower, SP was ineffective, but blocking glutamate enhanced the response in a proportion of rats. Attempts to understand and control immune activity in the CNS should take the local neurochemical environment into account.