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An adequately robust early TNF-α response is a hallmark of survival following trauma/hemorrhage

Namas, R and Ghuma, A and Torres, A and Polanco, P and Gomez, H and Barclay, D and Gordon, L and Zenker, S and Kim, HK and Hermus, L and Zamora, R and Rosengart, MR and Clermont, G and Peitzman, A and Billiar, TR and Ochoa, J and Pinsky, MR and Puyana, JC and Vodovotz, Y (2009) An adequately robust early TNF-α response is a hallmark of survival following trauma/hemorrhage. PLoS ONE, 4 (12).

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Abstract

Background: Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental. Methodology/Principal Findings: Paradoxically, plasma levels of the early inflammatory cytokine TNF-α (but not IL-6, IL-10, or NO2-/NO3-) were significantly elevated within 6 h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover, plasma TNF-α was inversely correlated with Marshall Score, an index of organ dysfunction, both in the 23 patients taken together and in the survivor cohort. Accordingly, we hypothesized that if an early, robust pro-inflammatory response were to be a marker of an appropriate response to injury, then individuals exhibiting such a response would be predisposed to survive. We tested this hypothesis in swine subjected to various experimental paradigms of T/HS. Twenty-three anesthetized pigs were subjected to T/HS (12 HS-only and 11 HS + Thoracotomy; mean arterial pressure of 30 mmHg for 45-90 min) along with surgery-only controls. Plasma obtained at pre-surgery, baseline post-surgery, beginning of HS, and every 15 min thereafter until 75 min (in the HS only group) or 90 min (in the HS + Thoracotomy group) was assayed for TNF-α, IL-6, IL-10, and NO2-/NO3-. Mean post-surgery±HS TNF-α levels were significantly higher in the survivors vs. non-survivors, while non-survivors exhibited no measurable change in TNF-α levels over the same interval. Conclusions/Significance: Contrary to the current dogma, survival in the setting of severe, acute T/HS appears to be associated with an immediate increase in serum TNF-α. It is currently unclear if this response was the cause of this protection, a marker of survival, or both. This abstract won a Young Investigator Travel Award at the SHOCK 2008 meeting in Cologne, Germany. © 2009 Namas et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Namas, R
Ghuma, A
Torres, A
Polanco, P
Gomez, Hheg18@pitt.eduHEG18
Barclay, Ddeb7@pitt.eduDEB7
Gordon, Llgordon@pitt.eduLGORDON
Zenker, S
Kim, HKhyk11@pitt.eduHYK11
Hermus, L
Zamora, Rzamorar@pitt.eduZAMORAR
Rosengart, MRmrr18@pitt.eduMRR18
Clermont, Gcler@pitt.eduCLER
Peitzman, Apeitzman@pitt.eduPEITZMAN
Billiar, TRbilliar@pitt.eduBILLIAR
Ochoa, J
Pinsky, MRpinsky@pitt.eduPINSKY
Puyana, JCjcp51@pitt.eduJCP51
Vodovotz, Yvodovotz@pitt.eduVODOVOTZ
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorOjcius, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 1 December 2009
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 4
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0008406
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
MeSH Headings: Animals; Disease Models, Animal; Female; Humans; Inflammation--blood; Inflammation--etiology; Male; Middle Aged; Nitrates--blood; Nitrites--blood; Shock, Hemorrhagic--blood; Shock, Hemorrhagic--complications; Survival Analysis; Sus scrofa; Thoracotomy; Time Factors; Tumor Necrosis Factor-alpha--blood
Other ID: NLM PMC2794373
PubMed Central ID: PMC2794373
PubMed ID: 20027315
Date Deposited: 03 Aug 2012 18:33
Last Modified: 09 Aug 2019 17:55
URI: http://d-scholarship.pitt.edu/id/eprint/13302

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