Sepsis is the leading cause of death in the ICU with an estimated 6 million victims per year worldwide. Although septic shock is traditionally viewed as an excessive systemic inflammatory reaction to invasive microbial pathogens, pharmacological suppression of the innate immune response in sepsis has proved to be unsuccessful. An important reason for this might be that the vast majority of septic patients survive the initial pro-inflammatory hit, but die in the subsequent immunosuppressed state due to secondary/opportunistic infections. This so-called 'immunoparalysis' is increasingly recognized as the overriding immune dysfunction in septic patients. Reversal of sepsis-induced immunoparalysis is therefore a promising adjunctive treatment for patients presenting with septic shock.~It was demonstrated that interferon-gamma (IFN)-gamma can reverse immunoparalysis in vitro and in vivo in animals and in healthy volunteers. Moreover, in a case-series of septic patients interferon-gamma treatment leaded to reversal of immunoparalysis, reduction in mechanical ventilation time and length of stay with no relevant side-effects.~The primary aim of this study is to assess the effects of adjunctive therapy with IFN-gamma on immune function in patients with septic shock in a placebo-controlled manner. Moreover, the investigators want to evaluate new markers that could be used to identify patients with immunoparalysis, and to monitor the patient's immunological response to IFN-γ. In addition, mechanistic studies will be performed to further elucidate mechanisms (such as epigenetic modifications) behind immunoparalysis and the effects of IFN-γ on these mechanisms.
The primary aim of this study is to assess the effects of adjunctive therapy with Interferon (IFN)-gamma on immune function in patients with septic shock in a placebo-controlled manner. Moreover, the investigators want to evaluate new markers that could be used to identify patients with immunoparalysis, and to monitor the patient's immunological response to IFN-γ. In addition, mechanistic studies will be performed to further elucidate mechanisms (such as epigenetic modifications) behind immunoparalysis and the effects of IFN-γ on these mechanisms. With use of the results the investigators will obtain in this pilot study, the investigators will conduct a large multicentre clinical trial with IFN-γ.