The adenosinergic immunomodulatory drugs.
Hypoxia-driven increase of extracellular adenosine in local tissue microenvironments of inflamed and cancerous tissues plays a critical role in the regulation of tissue destruction by activated immune cells. Accumulated data suggest that injection or consumption of A2A adenosine receptor (A2AR) antagonists may represent a drug treatment that diminishes adenosine-mediated immunosuppression. Since this, in turn, enhances the immune response, inhibition of adenosine-A2AR signaling may be a promising approach to enhance anti-tumor or anti-pathogen immune response. Patients with disorders characterized by excessive inflammation may be at risk to A2AR antagonists (e.g. caffeine) because of the effect to increase inflammatory damage secondary to enhanced immunity. On the other hand, enhancement of hypoxia-adenosinergic immunomodulatory pathways may be beneficial to prevent inflammatory tissue destruction.
Ohta
Akio
A
New England Inflammation and Tissue Protection Institute, Northeastern University, 113 Mugar Health Science Building, 360 Huntington Avenue, Boston, MA 02115, United States. a.ohta@neu.edu
Sitkovsky
Michail
M
D000241:Adenosine / Q000009:adverse effects / Q000502:physiology*; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D043705:Receptor, Adenosine A2A / Q000008:administration & dosage / Q000627:therapeutic use; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D058917:Adenosine A2 Receptor Antagonists; D007166:Immunosuppressive Agents; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D000241:Adenosine