The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitoryeffect of IL-1 beta on long term potentiation - A role for JNK

Several effects of the proinflammatory cytokine, interleukin-1 beta (IL-1 b eta), have been described in the central nervous system, and one area of th e brain where marked changes have been reported is the hippocampus. Among t hese changes are an IL-1 beta -induced inhibition of long term potentiation (LTP) in perforant path-granule cell synapses and an attenuation of glutam ate release in synaptosomes prepared from the hippocampus. Evidence suggest s that, at least in circulating cells, the anti-inflammatory cytokine, IL-1 0, antagonizes certain effects of IL-1. We investigated the effect of IL-10 on IL-1 beta -induced inhibition of LTP and glutamate release. The evidenc e presented indicates that IL-1 beta stimulates the stress-activated protei n kinase, c-Jun-activated protein kinase (JNK), and IL-1 receptor-associate d kinase, which may explain its inhibitory effect on release and LTP, and t hat IL-10 reversed the IL-10-induced stimulation of JNK activity and inhibi tion of release and LTP. We observed that IL-10 abrogated the stimulatory e ffect of IL-1 beta on superoxide dismutase activity and reactive oxygen spe cies production, whereas the H2O2-induced inhibition of LTP was also blocke d by IL-10. We present evidence that suggests that the action of IL-10 may be mediated by its ability to induce shedding of the IL-1 type I receptor.