All-or-nothing type biphasic cytokine production of human lymphocytes after exposure to Alzheimer's beta-amyloid peptide.
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.
Teixeira
Antônio L
AL
Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais (ICB-UFMG), Belo Horizonte, Minas Gerais, Brazil.
Reis
Helton J
HJ
Coelho
Fernanda M
FM
Carneiro
Daniel S
DS
Teixeira
Mauro M
MM
Vieira
Luciene B
LB
Mukhamedyarov
Marat A
MA
Zefirov
Andrey L
AL
Janka
Zoltán
Z
Palotás
András
A