Cell type-specific interleukin-1beta signaling in the CNS.

Interleukin-1beta (IL-1beta) is a potent and pleiotropic inflammatory cytokine that is highly produced in the CNS under conditions of damage, disease, or stress. This cytokine acts on CNS glia to effect inflammatory responses, mediated in part via activation of the nuclear factor-kappaB (NF-kappaB) transcription factor, and consequent induction of numerous cytokines. Neurons as well as astrocytes in the hippocampus also express the type 1 IL-1 receptor, indicating that this cytokine can influence neuronal function directly, yet IL-1beta does not induce production of cytokines in neurons as it does in glia. In contrast, IL-1beta regulates synaptic function of hippocampal neurons. Here we demonstrate that different signaling pathways mediate IL-1beta actions in neurons as compared with astrocytes. IL-1beta activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway and induces the activation of CREB in hippocampal neurons, in contrast to the activation of NF-kappaB in hippocampal astrocytes, demonstrating cell type-specific signaling responses to IL-1 in the brain and yielding distinct functional responses.