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Methylxanthines, Inflammation, and Cancer: Fundamental Mechanisms

  • Akio OhtaEmail author
  • Michail Sitkovsky
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 200)

Abstract

Methylxanthines are an integral part of everyday food and drink consumption even though the majority of humans do not identify them by their chemical name. The breakthrough in understanding the action(s) of methylxanthines was in large part due to the understanding that methylxanthines can function as antagonists of adenosine receptors. This represented an example of scientific search and was instructive in view of both new therapeutic options and alarming realizations. It was the subsequent demonstration of the in vivo critical role of A2A adenosine receptors in controlling excessive collateral inflammatory damage that attracted the attention of immunologists to the A2A-adenosine-receptor-antagonizing methylxanthines. We summarize here data showing that caffeine is capable of preventing the inhibition of antitumor T cells in a hypoxic tumor microenvironment. On the other hand, caffeine may exacerbate liver damage by weakening the tissue-protecting A2A adenosine receptor signaling during episodes of acute liver inflammation. However, methylxanthines may also prevent the excessive hepatic connective tissue deposition that is associated with the progression of chronic hepatitis to cirrhosis, which is one of the common causes of mortality.

Keywords

Adenosine Adenosine receptor Autoimmunity Caffeine Hepatitis Hypoxia Tumor 

Abbreviations

A2AR

A2A adenosine receptors

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

cAMP

Cyclic AMP

Con A

Concanavalin A

GGT

γ-Glutamyltransferase

LPS

Lipopolysaccharide

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Copyright information

© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, New England Inflammation and Tissue Protection InstituteNortheastern UniversityBostonUSA
  2. 2.Cancer Vaccine CenterDana-Farber Cancer Institute, Harvard Institutes of MedicineBostonUSA

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