| Immunosuppression in patients who die of sepsis and multiple organ failure. | |
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MedLine Citation:
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PMID: 22187279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Severe sepsis is typically characterized by initial cytokine-mediated hyperinflammation. Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting. OBJECTIVES: 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. RESULTS: 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 < .001 for all). There were similar reductions in 5-hour lipopolysaccharide-stimulated cytokine secretion. Cytokine secretion in sepsis patients was generally less than 10% that in controls, independent of age, duration of sepsis, corticosteroid use, and nutritional status. Although differences existed 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 sepsis patients vs cancer patients and vs 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 nonsepsis etiologies have biochemical, flow cytometric, and immunohistochemical findings consistent with immunosuppression. Targeted immune-enhancing therapy may be a valid approach in selected patients with sepsis. |
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Authors:
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Jonathan S Boomer; Kathleen To; Kathy C Chang; Osamu Takasu; Dale F Osborne; Andrew H Walton; Traci L Bricker; Stephen D Jarman; Daniel Kreisel; Alexander S Krupnick; Anil Srivastava; Paul E Swanson; Jonathan M Green; Richard S Hotchkiss |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: JAMA : the journal of the American Medical Association Volume: 306 ISSN: 1538-3598 ISO Abbreviation: JAMA Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-21 Completed Date: 2011-12-23 Revised Date: 2012-05-21 |
Medline Journal Info:
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Nlm Unique ID: 7501160 Medline TA: JAMA Country: United States |
Other Details:
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Languages: eng Pagination: 2594-605 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptive Immunity Aged Aged, 80 and over Case-Control Studies Cytokines / secretion* Female Flow Cytometry Humans Immune Tolerance* Immunity, Innate Immunohistochemistry Inflammation Intensive Care Units Lung / cytology Male Middle Aged Multiple Organ Failure / immunology*, mortality Sepsis / immunology*, mortality Spleen / cytology |
| Grant Support | |
ID/Acronym/Agency:
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GM44118/GM/NIGMS NIH HHS; GM55194/GM/NIGMS NIH HHS; HL104985/HL/NHLBI NIH HHS; R21 HL104985/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines |
| Comments/Corrections | |
Comment In:
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JAMA. 2011 Dec 21;306(23):2618-9
[PMID:
22187286
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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