An adequately robust early TNF-alpha response is a hallmark of survival following trauma/hemorrhage.
BACKGROUND
Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental.


RESULTS
Paradoxically, plasma levels of the early inflammatory cytokine TNF-alpha (but not IL-6, IL-10, or NO(2) (-)/NO(3) (-)) were significantly elevated within 6 h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover, plasma TNF-alpha 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-alpha, IL-6, IL-10, and NO(2) (-)/NO(3) (-). Mean post-surgery+/-HS TNF-alpha levels were significantly higher in the survivors vs. non-survivors, while non-survivors exhibited no measurable change in TNF-alpha levels over the same interval.


CONCLUSIONS
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-alpha. 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.
Namas
Rajaie
R
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ghuma
Ali
A
Torres
Andres
A
Polanco
Patricio
P
Gomez
Hernando
H
Barclay
Derek
D
Gordon
Lisa
L
Zenker
Sven
S
Kim
Hyung Kook
HK
Hermus
Linda
L
Zamora
Ruben
R
Rosengart
Matthew R
MR
Clermont
Gilles
G
Peitzman
Andrew
A
Billiar
Timothy R
TR
Ochoa
Juan
J
Pinsky
Michael R
MR
Puyana
Juan Carlos
JC
Vodovotz
Yoram
Y
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000150:complications; D016019:Survival Analysis; D034421:Sus scrofa; D013908:Thoracotomy; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha