These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-alpha supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.

Heat shock protein (HSP) synthesis arises transiently as a tool to protect cellular homeostasis after exposure to heat and a wide spectrum of stressful and potentially deleterious stimuli. HSPs are "molecular chaperones" that recognize and form a complex with incorrectly folded or denatured proteins, which ultimately leads to correct folding, compartmentalization, or degradation. Accumulating evidence has implicated HSPs as mediators of myocardial protection, particularly in experimental models of ischemia and reperfusion injury. Impaired myocardial performance, which results from many factors, including hypoxia, is one of the main mechanisms responsible for heart failure in the critically ill patient. In this setting, different protective functions have been attributed to HSPs, which include repairing ion channels, restoring redox balance, interacting with nitric oxide-induced protection, inhibiting proinflammatory cytokines, and preventing apoptosis pathway activation. On this basis, novel therapeutic strategies by means of promising pharmacologic interventions and/or gene transfection techniques are being investigated for their potential to enhance HSP expression by myocardial cells, with the goal of improving the outcome of the critically ill patient.

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