Background: Neuro-inflammation, triggered by beta-amyloid peptide, is implicated as one of the primary contributors to Alzheimer's disease (AD) pathogenesis, and several cytokines were identified as key instigating factors.
Methods: To reveal the inflammatory response of lymphocytes to the neuro-toxic beta-amyloid peptide, we evaluated the release of several cytokines from peripheral blood mononuclear cells with immuno-assays (ELISA). From hyper-acute to chronic effects of beta-amyloid peptide were assessed at a wide range of concentrations.
Results: The pro-inflammatory interleukin (IL)-1beta, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and Rantes (acronym for regulated on activation, normal T-cell expressed and secreted) as well as the pleiotropic IL-6 showed a biphasic release pattern over time in both low and high doses of amyloid treatment: after an initial increase, their concentration gradually fell to the baseline. The suppressors IL-4 and IL-10 had a sinus-like secretion panel: an acute increase in their levels turned to a depression and later followed by their over-secretion. Interestingly, beta-amyloid below 10(-8) mol/L produced no effect at all, but any molarity above this threshold caused the very same cytokine secretion pattern, the mark of an all-or-nothing response of beta-amyloid peptide.
Conclusions: These results delineate a highly organized pro- and anti-inflammatory response of cells to the neuro-toxic peptide. This is the first study to describe how the beta-amyloid-induced inflammatory processes in Alzheimer's dementia are regulated.