Interleukin-1beta enhances NMDA receptor-mediated current but inhibits excitatory synaptic transmission.

Interleukin (IL)-1beta is often characterized as the prototypic proinflammatory cytokine but is involved in various pathophysiological conditions in the central nervous system (CNS). A whole-cell recording technique was used to observe its effect on N-methyl-D-aspartate (NMDA)-evoked currents and spontaneous synaptic activity in cultured rat hippocampal neurons. The results showed that the frequencies but not the amplitudes of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC) were decreased by 10 or 100 ng/ml IL-1beta. IL-1beta at these concentrations also increased the NMDA receptor-mediated current. In addition, 10 ng/ml IL-1beta significantly increased the amplitude of the voltage-dependent Ca2+ current (I(Ca)). The increase in I(Ca) following treatment of cultures with IL-1beta resulted mainly from an increase in L-type current. These data suggest that IL-1beta modulates hippocampus-related functions via its effect on synaptic activity and Ca2+ signaling in neurons.