Boomer JS. JAMA. 2011;306:2594-2605.
Biochemical, flow cytometric and immunohistochemical
findings were consistent with immunosuppression in those who died of sepsis vs.
patients who died of nonsepsis etiologies, according to recent findings
published in the Journal of the American Medical Association.
ICU stay for patients with sepsis was a median of 8 days
compared with 4 or fewer days among control patients.
“Therapies that enhance the ability of the immune
system may be useful in sepsis,” Richard S. Hotchkiss, MD, of the
Washington University School of Medicine, told Infectious Disease News.
“It will be important to determine the immune phase of the septic patient;
if the patient is in the hypo-inflammatory phase of the disorder, drugs that
enhance host immunity might be effective in improving sepsis survival.”
Hotchkiss, in collaboration with Jonathan M. Green,
MD, and colleagues set out to examine the relationship between sepsis and
changes in immunity and immunosuppression.
Rapid postmortem spleen and lung tissue harvest were
conducted among 40 ICU patients (mean age of 71.7 years) who died of sepsis
between 2009 and 2011. Patients’ immune status at the time of death was
compared with spleens (n=29) and lungs (n=20) from control patients (mean age
of 52.7 years).
Cytokine secretion assays and immunophenotyping were
used to analyze potential mechanisms of immune dysfunction; immunohistochemical
staining determined immune effector cell loss.
Patients with sepsis stayed in the ICU for a median of 8
days compared with controls who stayed for 4 or fewer days. In sepsis patients,
cytokine secretion at 5 hours was less than 10% than that in controls —
independent of age, duration of sepsis, corticosteroid use and nutritional
status, according to the study.
Further, sepsis patients had significant depletion of
splenic cells and expression of ligands for inhibitory receptors on lung
epithelial cells. Conversely, increased expression of selected inhibitory
receptors and ligands and expansion of suppressor cell populations were
observed in the spleens and lungs of controls.
“These data provide a unique insight into the
status of the immune system during sepsis, not only in a lymphoid organ but in
peripheral tissue,” the researchers wrote. “Identification of
potential receptor ligand interactions and signaling pathways leading to
immunosuppression may allow for targeted therapeutic interventions to restore
“The traditional concept that deaths in sepsis were
due to a hyper-inflammatory, uncontrolled cytokine storm is too
simplistic,” Hotchkiss said. “Although some deaths are a result of
excessive inflammation, many deaths occur after the patient has progressed to a
state of immune exhaustion with a severely compromised immune system.”
Disclosure: This research was supported by NIH
grants GM44118, GM55194 and HL104985.