Interleukin-1β (IL-1β) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro

The effects of the cytokine, Interleukin-1β (IL-1β), and its receptor antagonist IL-1ra, were studied on long-term potentiation in the dentate gyrus of rat hippocampal slices. Field excitatory postsynaptic potentials were recorded extracellularly in the molecular region of the dentate gyrus in response to stimulation of the medial perforant path. Low frequency synaptic transmission was unaffected by IL-1β (1 ng/ml), but pre-treatment with IL-1β completely blocked induction of long-term potentiation. Co-application of IL-1β and IL-1ra (100 ng/ml) attenuated the inhibitory effect of IL-1β. In parallel with these findings, we demonstrate that IL-1fβ also inhibited 45Ca influx into the slices. The inhibitory effect of IL-1β on induction was mimicked by tumour necrosis factor (TNF; 4.5 ng/ml) and lipopolysaccharide (LPS; 10 μg/ml). These results indicate a modulatory role for cytokines in hippocampus and suggest that the inhibitory effect of IL-1β on long-term potentiation may relate to its inhibitory effect on calcium channel activity.