Lipopolysaccharide-induced increase in signalling in hippocampus is abrogated by IL-10--a role for IL-1 beta?

J Neurochem. 2004 Feb;88(3):635-46. doi: 10.1046/j.1471-4159.2003.02157.x.


Parenterally administered lipopolysaccharide (LPS) increases the concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the rat hippocampus and evidence suggests that this effect plays a significant role in inhibiting long-term potentiation (LTP). The anti-inflammatory cytokine IL-10, antagonizes certain effects of IL-1beta, so if the effects of LPS are mediated through an increase in IL-1beta, it might be predicted that IL-10 would also abrogate the effect of LPS. Here, we report that IL-10 reversed the inhibitory effect of LPS on LTP and the data couple this with an inhibitory effect on the LPS-induced increase in IL-1beta. LPS treatment increased hippocampal expression of IL-1 receptor Type I protein. Consistent with the LPS-induced increases in IL-1beta concentration and receptor expression, were downstream changes which included enhanced phosphorylation of IRAK and the stress-activated kinases, JNK and p38; these LPS-induced changes were reversed by IL-10, which concurs with the idea that these events are triggered by increased activation of IL-1RI by IL-1beta. We provide evidence which indicates that LPS treatment leads to evidence of cell death and this was reversed in hippocampus prepared from LPS-treated rats which received IL-10. The evidence is therefore consistent with the idea that IL-10 acts to protect neuronal tissue from the detrimental effects induced by LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Hippocampus / cytology
  • Hippocampus / enzymology
  • Hippocampus / immunology
  • Hippocampus / metabolism
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / metabolism
  • Interleukin-1 / physiology*
  • Interleukin-1 Receptor-Associated Kinases
  • Interleukin-10 / physiology*
  • JNK Mitogen-Activated Protein Kinases*
  • Lipopolysaccharides / pharmacology*
  • Long-Term Potentiation / immunology
  • MAP Kinase Kinase 4
  • MAP Kinase Signaling System / immunology*
  • Male
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / biosynthesis
  • Sialoglycoproteins / metabolism
  • Up-Regulation / immunology*
  • p38 Mitogen-Activated Protein Kinases


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • Interleukin-10
  • Protein Kinases
  • Interleukin-1 Receptor-Associated Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases