All-or-Nothing Type Biphasic Cytokine Production of Human Lymphocytes After Exposure to Alzheimer's β-Amyloid Peptide

Antônio L. Teixeira, Helton J. Reis, Fernanda M. Coelho, Daniel S. Carneiro, Mauro M. Teixeira, Luciene B. Vieira, Marat A. Mukhamedyarov, Andrey L. Zefirov, Zoltán Janka, András Palotás

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background: Neuro-inflammation, triggered by β-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 β-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 β-amyloid peptide were assessed at a wide range of concentrations. Results: The pro-inflammatory interleukin (IL)-1β, tumor necrosis factor-α, 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, β-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 β-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 β-amyloid-induced inflammatory processes in Alzheimer's dementia are regulated.

Original languageEnglish (US)
Pages (from-to)891-895
Number of pages5
JournalBiological Psychiatry
Volume64
Issue number10
DOIs
StatePublished - Nov 15 2008
Externally publishedYes

Keywords

  • β-amyloid peptide
  • Alzheimer's disease
  • cytokine
  • interleukin
  • lymphocyte

ASJC Scopus subject areas

  • Biological Psychiatry

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