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Journal of Neural Transmission

, Volume 111, Issue 3, pp 441–447 | Cite as

Pentoxyphylline and propentophylline are inhibitors of TNF-α release in monocytes activated by advanced glycation endproducts

  • I. Meiners
  • S. Hauschildt
  • K. Nieber
  • G. Münch
Short Communication

Summary.

Non-enzymatic glycation of proteins with reducing sugars and subsequent transition metal-catalyzed oxidation leads to the formation of protein-bound “advanced glycation endproducts” (AGEs). They accumulate on long-lived protein deposits inducing senile plaques in Alzheimer’s disease. AGE-modified proteins are able to activate microglia and astroglia and can cause chronic inflammation. The aim of the present study was to confirm the stimulatory effect of different AGEs on TNF-α release in human monocytes. Furthermore, the effects of four xanthine derivatives on AGE-induced TNF-α release were investigated. We show that chicken egg albumin-AGEs prepared with glucose and chicken egg albumin-AGEs prepared with methylglyoxal dose-dependently induce TNF-α release. The xanthine derivatives pentoxyphylline and propentophylline attenuate AGE-induced TNF-α release in a dose-dependent manner. Theophylline at low concentrations slightly stimulated TNF-α release whereas caffeine had no effect. The inhibition of the AGE-induced TNF-α release by pentoxyphylline and propentophylline provides interesting pharmacological strategies for diseases with local neuroinflammation such as Alzheimer’s disease.

Keywords: Advanced glycation endproducts, tumor necrosis factor, xanthine, Alzheimer’s disease. 

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Copyright information

© Springer-Verlag/Wien 2003

Authors and Affiliations

  • I. Meiners
    • 1
  • S. Hauschildt
    • 2
  • K. Nieber
    • 3
  • G. Münch
    • 1
  1. 1.Nachwuchsgruppe Neuroimmunologische ZellbiologieIZKF LeipzigGermany
  2. 2.Abteilung Immunbiologie, Institut für ZoologieGermany
  3. 3.Abteilung Pharmakologie für Naturwissenschaftler, Institut für Pharmazie, Universität LeipzigLeipzigGermany

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