Interleukin-6, β-amyloid peptide and NMDA interactions in rat cortical neurons

Neuronal damage in Alzheimer's disease (AD) is thought to involve direct toxicity of β-amyloid peptide (Aβ) and excitotoxicity involving NMDA receptors (NMDARs) and altered Ca 2+ dynamics. Inflammation agents produced by microglia or astrocytes and associated with senile plaques such as the cytokine interleukin-6 (IL-6) could also contribute. To investigate this possibility, neuronal damage (lactate dehydrogenase assay, LDH, assay) was measured in cultures of rodent cortical neurons chronically treated with IL-6, Aβ or Aβ plus IL-6 and acutely treated with NMDA. Both Aβ and NMDA produced neuronal damage and this effect was larger with combined treatment. IL-6 did not produce significant neuronal damage but the largest neuronal damage was observed in cultures exposed to all three factors. IL-6 and Aβ enhanced Ca 2+ responses to NMDA and combined treatment produced the largest effect. These results are consistent with a role for interactions between Aβ, NMDA and IL-6 in the neuronal loss in AD.