Protective effect of an adenosine kinase inhibitor in septic shock.

摘要: Adenosine exhibits potent anti-inflammatory activities but its therapeutic use is limited by cardiovascular side effects. Inhibitors of an enzyme involved in adenosine metabolism, kinase (EC 2.7.1.20), were evaluated for their ability to enhance endogenous production. One novel inhibitor, GP-1-515, was studied two models septic shock assess protective GP-1-515 significantly decreased mortality mice that received a lethal i.v. injection endotoxin. The beneficial effect accompanied neutrophil accumulation the lungs and reversed receptor antagonist, implying effects mediated adenosine. Plasma levels TNF-alpha, not IL-1 alpha or IL-6, lower GP-1-515-treated animals. In second model sepsis, increased survival bacterial peritonitis rats. mechanism action both likely multifactorial, including adenosine-mediated inhibition adhesion, cytokine production, oxygen radical generation. inhibitors have vitro vivo represent approach treatment inflammatory diseases.