Interleukin-1β causes long-term potentiation deficiency in a mouse model of septic encephalopathy.

Sepsis induces multiple organ dysfunction syndrome including septic encephalopathy (SE), which results in cognitive impairment. However, an effective treatment for SE remains unknown. We determined the role of interleukin-1β (IL-1β) in long-term potentiation (LTP) deficiency after SE. At first, endotoxin level in the blood was increased at 24 h after cecum ligation and puncture (CLP) (i.e. SE model). Second, the expression of IL-1β and its receptor in the hippocampus was determined by immunohistochemistry and immunoblotting. The number of Iba1-positive cells and their expression of IL-1β were enhanced by CLP with disruption of the blood brain barrier. Also, Iba1, IL-1β, and occludin protein expressions were consistent with immunohistochemical results. Third, we used an electrophysiological technique and observed the LTP deficiency, a hallmark of learning and memory, in the slices of hippocampus after CLP. Since type 1 interleukin-1 receptors (IL-1R1s) on neuronal cells were increased in the hippocampus, we utilized IL-1R1 antagonist. Pre-incubation with IL-1R1 antagonist for 30 min before recording of field excitatory post-synaptic potentials (fEPSPs) in the hippocampus canceled LTP deficiency after CLP. These results suggest the novel importance of IL-1β in synaptic plasticity deficiency associated with sepsis-induced brain inflammation. In a mouse model of SE, IL-1R1 inhibition is important in protecting synaptic function of the hippocampus after induction of SE.