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Immune enhancing therapy needed in sepsis patients
Boomer JS. JAMA. 2011;306:2594-2605.
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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 host immunity.”
“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.
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