DOI 10.1007/s00702-003-0066-y J Neural Transm (2004) 111: 441–447 Pentoxyphylline and propentophylline are inhibitors of TNF-a release in monocytes activated by advanced glycation endproducts Short Communication I. Meiners 1 , S. Hauschildt 2 , K. Nieber 3 , and G. Mu ¨nch 1 1 Nachwuchsgruppe Neuroimmunologische Zellbiologie, IZKF Leipzig, 2 Abteilung Immunbiologie, Institut f€ ur Zoologie, and 3 Abteilung Pharmakologie f€ ur Naturwissenschaftler, Institut f€ ur Pharmazie, Universit € at Leipzig, Leipzig, Germany Received July 24, 2003; accepted September 11, 2003 Published online December 3, 2003; # Springer-Verlag 2003 Summary. Non-enzymatic glycation of proteins with reducing sugars and sub- sequent 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-a release in human monocytes. Furthermore, the effects of four xanthine derivatives on AGE-induced TNF-a release were inves- tigated. We show that chicken egg albumin-AGEs prepared with glucose and chicken egg albumin-AGEs prepared with methylglyoxal dose-dependently induce TNF-a release. The xanthine derivatives pentoxyphylline and propento- phylline attenuate AGE-induced TNF-a release in a dose-dependent manner. Theophylline at low concentrations slightly stimulated TNF-a release whereas caffeine had no effect. The inhibition of the AGE-induced TNF-a 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. Abbreviations TNF-a tumor necrosis factor alpha, NO nitric oxide, LPS lipopolysacchaide, CEA chicken egg albumin, AGE advanced glycation endproducts, IL-1