Early immune anergy towards recall antigens and mitogens in patients at onset of septic shock

The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered with www.clinicaltrials.gov (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °C in vitro with bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset. Recall-antigen stimulation led to a severe dampening of normal cytokine release. This immunologic anergy was similarly observed after mitogen stimulation. Moreover, patients under hydrocortisone therapy or with lowered arterial oxygen tension had further reductions in cytokine levels upon B- and T-cell mitogen stimulation. This investigation reveals an early onset of immunoparalysis during sepsis. This immune incompetence in mounting an adequate response to further infections includes previously sensitized pathogens, as seen with recall-antigens. Also, the immune-suppressive role of hydrocortisone and low PaO(2) is highlighted. Aside from early broad-spectrum antimicrobial therapy, our findings reinforce the need for maximal immunological support and protection against further infections at the onset of sepsis.