The Janus faced role of secreted spingomyelinase and its inhibition in host response The increase in acid sphingomyelinase (aSMase) activity has been implicated in the severity of disease and its fatal outcome. In sepsis aSMase activity has been shown to continuously increase throughout the continuum from SIRS (systemic inflammatory response syndrome) to severe sepsis. The inhibition of this enzyme with desipramine a low molecular weight inhibitor presents promising results in cystic fibrosis patients. We therefore addressed the question of whether secreted aSMase is involved in host response to infection which is reflected in humoral and functional parameters of immune activation. We identified a dual function of this enzyme in host response where the activity of aSMase is essential during the early phase of host response with respect to bacterial elimination yet the continuous increase in aSMase activity and ceramide generation presents with detrimental effects in the late phase of host response. ...