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Cited by 11Sepsis Diagnosis and TreatmentInflammation biomarkers and pathwaysImmune Response and Inflammation

Towards personalized medicine in sepsis: quest for Shangri-La?

Open access
Sen, Ayan, Yende, Sachin·2013·Critical Care
DOI 10.1186/cc12485PMC PMC4056785
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Abstract

Citation Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD 2nd, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS: Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011, 306: 2594-2605. Background Severe sepsis is typically characterized by initial cytokine-mediated hyper-inflammation. Whether this hyper-inflammatory phase is followed by immunosuppression is a subject of controversy. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting. Methods Objectives To determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression. Design Rapid prospective postmortem spleen and lung tissue harvest and analysis within 120 minutes of death. Setting Intensive care units (ICUs) of academic medical centers. Subjects A convenience sample of 40 patients who died with active severe sepsis was taken over the course of 2 years to characterize their immune status at the time of death. 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. Interventions None. Outcomes 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. Results The mean ages (standard deviations) of patients with sepsis and controls were 71.7 (15.9) and 52.7 (15.0) years, respectively. Patients with sepsis were in the ICU for a median of 8 days (range of 1 to 195 days), whereas control patients were in the ICU for not more than 4 days. The median duration of sepsis was 4 days (range of 1 to 40 days). Anti-CD3/anti-CD28-stimulated splenocytes from patients with sepsis, compared with those from controls, had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5,361 (95% confidence interval (CI) 3,327 to 7,485) pg/mL versus 418 (95% CI 98 to 738) pg/mL; interferon-gamma, 1,374 (95% CI 550 to 2,197) pg/mL versus 37.5 (95% CI -5 to 80) pg/mL; interleukin-6, 3,691 (95% CI 2,313 to 5,070) versus 365 (95% CI 87 to 642) pg/mL; and interleukin-10, 633 (95% CI -269 to 1,534) versus 58 (95% CI -39 to 156) pg/mL (P < 0.001 for all). There were similar reductions in 5-hour lipopolysaccharidestimulated cytokine secretion. Cytokine secretion in patients with sepsis was generally less than 10% of that in controls, independently of age, duration of sepsis, corticosteroid use, and nutritional status. Despite differences between spleen and lung, flow cytometric analysis showed increased expression of selected inhibitory receptors and ligands and expansion of suppressor cell populations in both organs. Unique differences in cellular inhibitory molecule expression existed in immune cells isolated from lungs of patients with sepsis versus patients with cancer and versus transplant donors. Immunohistochemical staining showed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells. Conclusions Patients who die in the ICU following sepsis compared with patients who die of non-sepsis etiologies have bio-chemical, flow cytometric, and immunohistochemical findings consistent with those of immunosuppression. Targeted immune-enhancing therapy may be a valid approach in selected patients with sepsis.

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  • Most studies and reviews of precision medicine in critical illness focus on host genetics, immune responses, and exposures.

    “Most studies and reviews of precision medicine in critical illness, however, focus on host genetics, immune responses, and exposures.153–155”

    From The microbiome and critical illness (2016) · cites this paper as [155]

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Authors
Sen, A., & Yende, S.
Affiliations
University of Pittsburgh (US)
Corresponding author
Yende, Sachin
ORCID
Venue
Critical Care
Publisher
Springer Science and Business Media LLC
Published
2013
Volume
17
Issue
1
Pages
303
ISSN
1364-8535 (ISSN-L)
DOI
10.1186/cc12485
PMC
PMC4056785
OpenAlex
W2018145440
Cited by
11
References
19
Citations by year
2026: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2015: 2 · 2014: 2 · 2013: 1
Type
book review
Language
en
Open access
Locations
  • Critical Care (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
severe sepsis, immunosuppression, multiple organ failure, cytokine production, T cell dysfunction, anti-CD3/CD28 stimulation, T cell receptor signaling, CD4+ T cells, CD8+ T cells, B cells, natural killer cells, innate immunity, adaptive immunity, cytokine storm, personalized medicine
MeSH terms
Female, Humans, Immune Tolerance, Male, Multiple Organ Failure, Cytokines, Sepsis

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