Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock

Abstract

In septic shock, the anti-inflammatory effects of catecholamines are blunted by downregulation of beta2-ARs and upregulation of the inhibitory G protein in CD14+ monocytes. Beta-adrenergic downregulation is overcome by inhibitors of PDE4. These results provide a mechanistic rationale for the therapeutic use of selective PDE4 inhibitors in the treatment of septic shock.