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Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the genetic and inflammatory markers of sepsis (GenIMS) study

Kellum, JA and Kong, L and Fink, MP and Weissfeld, LA and Yealy, DM and Pinsky, MR and Fine, J and Krichevsky, A and Delude, RL and Angus, DC (2007) Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the genetic and inflammatory markers of sepsis (GenIMS) study. Archives of Internal Medicine, 167 (15). 1655 - 1663. ISSN 0003-9926

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Background: Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of proinflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods: This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results: A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8-39.0) (P<.001). Conclusions: The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest when both proinflammatory and antiinflammatory cytokine levels are high. ©2007 American Medical Association. All rights reserved.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kellum, JAkellum@pitt.eduKELLUM0000-0003-1995-2653
Kong, L
Fink, MP
Weissfeld, LA
Yealy, DMdmy@pitt.eduDMY
Pinsky, MRpinsky@pitt.eduPINSKY0000-0001-6166-700X
Fine, J
Krichevsky, A
Delude, RL
Angus, DCangusdc@pitt.eduANGUSDC0000-0002-7026-5181
Date: 13 August 2007
Date Type: Publication
Journal or Publication Title: Archives of Internal Medicine
Volume: 167
Number: 15
Page Range: 1655 - 1663
DOI or Unique Handle: 10.1001/archinte.167.15.1655
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
ISSN: 0003-9926
PubMed ID: 17698689
Date Deposited: 05 Mar 2012 17:18
Last Modified: 30 Jan 2020 16:55


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