Interleukin-1 receptor antagonist exerts agonist activity in the hippocampus independent of the interleukin-1 type I receptor.

Authors: Loscher, CE  Mills, KH  Lynch, MA 
Citation: Loscher CE, etal., J Neuroimmunol. 2003 Apr;137(1-2):117-24.
Pubmed: (View Article at PubMed) PMID:12667655

Interleukin-1 receptor antagonist (IL-1ra) selectively and competitively inhibits the actions of IL-1 at its receptors and has not been reported to have agonist activity. This study demonstrates that stimulation of synaptosomes with IL-1ra in vitro, mimicked the effects of IL-1 beta by decreasing glutamate release and increasing JNK phosphorylation. These effects of IL-1ra, but not IL-1 beta, were maintained in IL-1 type I receptor (IL-1RI) defective mice. IL-1 beta blocked these IL-1ra-induced effects suggesting that it may also act independently of IL-1RI in some circumstances. Furthermore, IL-1ra mimicked the inhibitory effect of IL-1 beta on long-term potentiation (LTP) in the hippocampus. These data, taken together with our findings that IL-1ra binds to hippocampal synaptosomes in the absence of IL-1RI, provide evidence that IL-1ra exerts agonist activity in the hippocampus independent of IL-1RI.

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RGD Object Information
RGD ID: 1626684
Created: 2007-08-17
Species: All species
Last Modified: 2007-08-17
Status: ACTIVE