Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure

To determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression. DESIGN, SETTING, AND PARTICIPANTS: Rapid postmortem spleen and lung tissue harvest was performed at the bedsides of 40 patients who died in intensive care units (ICUs) of academic medical centers with active severe sepsis to characterize their immune status at the time of death (2009–2011). Control spleens (n=29) were obtained from patients who were declared brain-dead or had emergent splenectomy due to trauma; control lungs (n=20) were obtained from transplant donors or from lung cancer resections. MAIN OUTCOME MEASURES: Cytokine secretion assays and immunophenotyping of cell surface receptor-ligand expression profiles were performed to identify potential mechanisms of immune dysfunction. Immunohistochemical staining was performed to evaluate the loss of immune effector cells.

The mean ages of patients with sepsis and controls were 71.7 (SD, 15.9) and 52.7 (SD, 15.0) years, respectively. The median number of ICU days for patients with sepsis was 8 (range, 1–195 days), while control patients were in ICUs for 4 or fewer days. The median duration of sepsis was 4 days (range, 1–40 days). Compared with controls, anti-CD3/anti-CD28–stimulated splenocytes from sepsis patients had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5361 (95% CI, 3327–7485) pg/mL vs 418 (95% CI, 98–738) pg/mL; interferon γ, 1374 (95% CI, 550–2197) pg/mL vs 37.5 (95% CI, −5 to 80) pg/mL; interleukin 6, 3691 (95% CI, 2313–5070) vs 365 (95% CI, 87–642) pg/mL; and interleukin 10, 633 (95% CI, −269 to 1534) vs 58 (95% CI, −39 to 156) pg/mL; (P