The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK

Several cytokines have short-term effects on synaptic transmission and plas ticity that are thought to be mediated by the activation of intracellular p rotein kinases. We have studied the effects of interleukin-6 (IL-6) on the expression of paired pulse facilitation (PPF), posttetanic potentiation (PT P), and long-term potentiation (LTP) in the CA1 region of the hippocampus a s well as on the activation of the signal transducer and activator of trans cription-3 (STAT3), the mitogen-activated protein kinase ERK (MAPK/ERK), an d the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). IL-6 induced a marked and dose-dependent decrease in the expression of PTP and LTP that could be counteracted by the simultaneous treatment with the tyrosine kinase inhibitor lavendustin A (LavA) but did not significantly af fect PPF. The IL-6-induced inhibition of PTP and LTP was accompanied by a s imulation of STAT3 tyrosine phosphorylation and an inhibition of MAPK/ERK d ual phosphorylation, in the absence of changes in the state of activation o f SAPK/JNK. Both effects of IL-6 on STAT3 and MAPK/ERK activation were effe ctively counteracted by LavA treatment. The results indicate that tyrosine kinases and MAPK/ERK are involved in hippocampal synaptic plasticity and ma y represent preferential intracellular targets for the actions of IL-6 in t he adult nervous system.