IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro.
It has been shown that Abeta inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1beta. Abeta also increases microglial activation, which is the likely cell source of IL-1beta. Because IL-4 attenuates the effects of IL-1beta in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Abeta on LTP and IL-1beta concentration. Following treatment with Abeta, IL-4 or minocycline, rats were assessed for their ability to sustain LTP in perforant path-granule cell synapses. We report that the Abeta-induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL-1beta concentration, and that these changes were attenuated by treatment of rats with IL-4 and minocycline. We also report that Abeta-induced increases in expression of MHCII and IL-1beta were similarly attenuated by IL-4 and minocycline in glial cultures prepared from neonatal rats. These data suggest that glial cell activation and the consequent increase in IL-1beta concentration mediate the inhibitory effect of Abeta on LTP and indicate that IL-4, by down-regulating glial cell activation, antagonizes the effects of Abeta.
Lyons
Anthony
A
Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin, Ireland.
Griffin
Rebecca J
RJ
Costelloe
Ceire E
CE
Clarke
Rachael M
RM
Lynch
Marina A
MA
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004347:Drug Interactions; D004660:Encephalitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D005802:Genes, MHC Class II / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000627:therapeutic use*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008911:Minocycline / Q000627:therapeutic use; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D053583:Interleukin-1beta; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015847:Interleukin-4; D008911:Minocycline