• Palle Toft and Else Tønnesen.
• Odense University Hospital, DK-5000 Odense C, Denmark.
• Expert Rev Clin Pharmacol. 2011 Jul 1;4(4):491-501.

AbstractCritically ill patients with severe sepsis and septic shock are characterized by a systemic inflammatory response consisting of pro- and anti-inflammatory mediators. Owing to the high mortality of severe sepsis, great efforts have been undertaken within the last 30 years to develop an immune-modulating therapy to improve survival. Relatively few pharmacological immune-modulating interventions have demonstrated a beneficial impact on survival, while other studies have shown a detrimental effect of such interventions. Among the immune-modulating interventions tested, activated protein C and intensive insulin therapy have been shown to improve survival in septic patients. However, in later studies, it has been difficult to reproduce these beneficial effects. There appears to be a discrepancy between the promising effects of immune-modulating interventions in animal studies and the effects seen in the clinical setting. In the future, the onset of the proinflammatory versus the anti-inflammatory response must be better defined and the timing of treatment with immune-modulating agents should be better managed.

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