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      Attenuation of LPS-Induced Changes in Synaptic Activity in Rat Hippocampus by Vasogen’s Immune Modulation Therapy

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          Systemic injection of lipopolysaccharide (LPS) blocks the expression of long-term potentiation in the hippocampus of the rat. This is coupled with increased IL-1β concentration and c-Jun NH<sub>2</sub>-terminal kinase activity, as well as an increase in the number of cells displaying apoptotic characteristics in the hippocampus. Vasogen’s Immune Modulation Therapy (IMT) is a procedure involving intramuscular administration of syngeneic blood which has been exposed ex vivo to elevated temperature, oxidation and ultraviolet light. We report that Vasogen’s IMT significantly abrogates these LPS-induced effects with a concomitant increase in the concentration of the anti-inflammatory cytokine IL-10. These data suggest that Vasogen’s IMT may play a protective role against the deleterious effects of immune insults in the brain.

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

          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.
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            Effects of vagotomy on lipopolysaccharide-induced brain interleukin-1β protein in rats


              Author and article information

              S. Karger AG
              August 2002
              30 August 2002
              : 10
              : 1
              : 40-46
              aDepartment of Physiology, Trinity College, Dublin, Ireland; bVasogen Inc., Toronto, Canada
              64413 Neuroimmunomodulation 2002–03;10:40–46
              © 2002 S. Karger AG, Basel

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              Page count
              Figures: 5, References: 25, Pages: 7
              Original Paper


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