Cyclic adenosine monophosphate signaling and organ dysfunction in septic shock

Abstract

Herein we review some of the existing knowledge on how the intracellular signaling mediator cyclic adenosine monophosphate (cAMP) regulates mechanisms involved in sepsis and septic shock, focusing on inflammation and hemodynamics. Elevating cAMP by inhibition of the cAMP-hydrolyzing phosphodiesterases has been reported to protect organ function in animal models of systemic inflammation and endotoxic shock and, likewise, increased survival from septic shock has been reported in mice deficient in specific cAMP phosphodiesterase isoforms. The cAMP signaling pathway modulates inflammation by attenuating proinflammatory cytokine release, neutrophil infiltration, degranulation and cytotoxic responses. cAMP also controls hemodynamics by regulating cardiovascular function, endothelial barrier function and platelet activation. There is a need to obtain a more detailed understanding of cAMP signaling, and to further evaluate the future potential of sepsis treatment targeting this pathway.