Immunomodulation in sepsis

Introduction. The systemic inflammatory response syndrome is induced by a strong inflammatory reaction which is called sepsis when it is caused by an infection. However, anti-inflammatory therapeutic strategies in septic patients were not successful, indicating a more complex system. It is now clear that systemic hyper-inflammation induces systemic anti- or hypo-inflammation which can lead to total paralysis of the immune system (immunoparalysis). Methods. Several studies were performed to evaluate parameters for describing the patient's immunocompetence. Based on these parameters, pilot trials were initiated to test immunomodulating therapies depending on the patient's immunocompetence. Results. The measurement of monocytic HLA-DR expression, as well as the measurement of ex vivo LPS-incluced TNF-a secretion, are suitable to describe the patient's immunocompetence. In addition to classical inflammation markers, the characterization of the inflammatory and infection status is completed by measurement of the plasma cytokines, LBP and PCT. IFN-g or GM-CSF application as well as the removal of inhibitory plasma mediators by hemofiltration/plasmapheresis can reconstitute the immune function in patients with immunoparalysis Conclusions. Immunomodulating therapeutic strategies in septic patients have to orientate on the patient's immunocompetence and inflammatory as well as infectious status: a patient in a hyper-inflammatory phase may need anti-inflammatory therapy whereas a patient in immunoparalysis needs immunoreconstitution/immunostimulating therapy.