Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na(+) channel is essential for the excitability and electrical properties of neurons. However, it is not known whether IL-1β directly affects the central Na(+) channels. In the present study, we examined the effects of IL-1β on Na(+) currents in cultured cortical neurons using patch-clamp recording. Our results showed that IL-1β suppressed Na(+) currents through its receptor in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. PKC and then p38 MAPK were involved in this inhibition. The spike amplitude was also inhibited by IL-1β in the doses that decreased the Na(+) currents. Our findings revealed the inhibition of chronic IL-1β treatment on voltage-gated Na(+) channels in the CNS, and showed that the action potential (AP) amplitude was reduced by IL-1β due to a decrease of Na(+) currents.