Abstract
Several effects of the proinflammatory cytokine, interleukin-1 beta (IL-1 beta), have been described in the central nervous system, and one area of the brain where marked changes have been reported is the hippocampus. Among these changes are an IL-1 beta-induced inhibition of long term potentiation (LTP) in perforant path-granule cell synapses and an attenuation of glutamate release in synaptosomes prepared from the hippocampus. Evidence suggests that, at least in circulating cells, the anti-inflammatory cytokine, IL-10, 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 evidence presented indicates that IL-1 beta stimulates the stress-activated protein kinase, c-Jun-activated protein kinase (JNK), and IL-1 receptor-associated kinase, which may explain its inhibitory effect on release and LTP, and that IL-10 reversed the IL-1 beta-induced stimulation of JNK activity and inhibition of release and LTP. We observed that IL-10 abrogated the stimulatory effect of IL-1 beta on superoxide dismutase activity and reactive oxygen species production, whereas the H(2)O(2)-induced inhibition of LTP was also blocked 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.
Highlights
Several effects of the proinflammatory cytokine, interleukin-1 (IL-1), have been described in the central nervous system, and one area of the brain where marked changes have been reported is the hippocampus
Data from previous experiments indicated that IL-1 inhibited KCl-stimulated [3H]glutamate release in hippocampus [7] and that increased Jun-activated protein kinase (JNK) activity was coupled with decreased endogenous glutamate release [14, 16]; we analyzed the effect of IL-1 (1 ng/ml) alone and in the presence of IL-10 (10 ng/ml) on endogenous glutamate release
We set out to investigate whether the anti-inflammatory cytokine, IL-10, might reverse the inhibitory effects of the proinflammatory cytokine, IL-1, on synaptic function in the hippocampus
Summary
Interleukin-1 (IL-1) is a proinflammatory cytokine that is released from antigen-presenting cells during infection or inflammation, and its effects were originally considered to be confined to the immune system, it is known to exert profound effects in the central nervous system These effects include modulation of thermoregulation, sleep, and appetite, which are perhaps consistent with the relatively high expression of the signal-generating IL-1 type 1 receptors (IL-1R1) in. The data indicate that IL-10 abrogates the IL-1-induced inhibition of glutamate release and LTP and its stimulatory effect on JNK We propose that this action of IL-10 may be mediated by its ability to prevent reactive oxygen species production by IL-1
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