Therapeutic Implications of Immunoparalysis in Critically Ill Patients

In opposite to the classic view of the systemic inflammatory response, there is increasing evidence that, during critical illness, there is a systemic antiinflammatory state intended to avoid the spread of the local proinflammatory response. The resulting immunosupression increases the risk of nosocomial infections, and has been related to an increase in morbidity and mortality in critically ill patients. Monocytes play a key role in orchestrating the inflammatory response, and a functional impairment of this population is the responsible for these phenomena. The decreased surface expression of class II molecules of the Main Histocompatibility Complex is both a marker of this state and a pathogenetic mechanism, as it decreases the antigen presentation capabilities of the mononuclear phagocytes. There are some therapeutic strategies to overcome this situation. Cytokines like IFNγ or GM-CSF have been tested in animal models and patients, but there are no conclusive data. Other drugs like Flt3, AS101 or antibodies against IL-10 have been tested only in experimental models. The development of a new framework on the inflammatory response, the need for a consensus in immune monitoring and the development of experimental and clinical trials are required to improve the outcome of severe patients with systemic injuries.