Authors: Rajaie Namas, Ali Ghuma, Andres Torres, Patricio Polanco, Hernando Gomez, Derek Barclay, Lisa Gordon, Sven Zenker, Hyung Kook Kim, Linda Hermus, Ruben Zamora, Matthew R. Rosengart, Gilles Clermont, Andrew Peitzman, Timothy R. Billiar, Juan Ochoa, Michael R. Pinsky, Juan Carlos Puyana, Yoram Vodovotz
Title: An Adequately Robust Early TNF-a Response Is a Hallmark of Survival Following Trauma/Hemorrhage
Summary: Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental. Paradoxically, plasma levels of the early inflammatory cytokine TNF-a (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-a 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-a, IL-6, IL-10, and NO2-/NO3-. Mean post-surgery6HS TNF-a levels were significantly higher in the survivors vs. nonsurvivors, while non-survivors exhibited no measurable change in TNF-a levels over the same interval. 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-a. It is currently unclear if this response was the cause of this protection, a marker of survival, or both.
Source: PLoS ONE 2009. 4:e8406.