The Anti-inflammatory Cytokine, Interleukin (IL)-10, Blocks the Inhibitory Effect of IL-1β on Long Term Potentiation

• Published in: The Journal of biological chemistry 2001-12, Vol.276 (49), p.45564
• Main Authors: Áine Kelly, Aileen Lynch, Emily Vereker, Yvonne Nolan, Patrice Queenan, Elizabeth Whittaker, Luke A. J. O'Neill, Marina A. Lynch
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M108757200

Several effects of the proinflammatory cytokine, interleukin-1β (IL-1β), 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-1β-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-1β-induced inhibition of LTP and glutamate release. The evidence presented indicates that IL-1β 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-1β-induced stimulation of JNK activity and inhibition of release and LTP. We observed that IL-10 abrogated the stimulatory effect of IL-1β 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.