PMID- 21464065
OWN - NLM
STAT- MEDLINE
DCOM- 20110811
LR  - 20151119
IS  - 1525-1489 (Electronic)
IS  - 0885-0666 (Linking)
VI  - 26
IP  - 2
DP  - 2011 Mar-Apr
TI  - Mortality in patients with septic shock correlates with anti-inflammatory but not 
      proinflammatory immunomodulatory molecules.
PG  - 125-32
LID - 10.1177/0885066610384465 [doi]
AB  - BACKGROUND: Mortality in patients with septic shock remains unacceptably high and 
      the attempts to antagonize certain proinflammatory cytokines based on the results 
      of animal model studies have failed to improve survival rates. The objective of 
      this article is to examine the pro-/anti-inflammatory cytokine balance in 
      patients with septic shock and its connection with mortality. METHODS: Serum 
      levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin 
      1beta [IL-1beta], interferongamma [IFN-gamma], and IL-6) and soluble cytokine antagonists 
      (soluble TNF receptor I [sTNF-RI], sTNF-RII, and IL-1Ra) were determined on 
      admission to the intensive care unit (ICU) and 3, 7, 14, and 28 days later in 52 
      patients with septic shock and in 36 healthy controls. Specific sandwich 
      enzyme-linked immunosorbent assay (ELISA) was used for all determinations. 
      RESULTS: Serum levels of most of the pro- and anti-inflammatory molecules 
      examined (TNF-alpha, IL-6, sTNF-RI, sTNF-RII, and IL-1 receptor agonist [IL-1Ra]) 
      were significantly elevated on admission and during the 28-day observation period 
      in patients when compared to controls. Notably, the anti-inflammatory mediators 
      sTNF-RI, sTNF-RII, and IL-1Ra were better predictors of mortality. 
      Receiver-operating characteristic (ROC) analysis revealed that sTNF-RI or 
      sTNF-RII concentrations over 2767 or 4619 pg/mL, respectively, determined a high 
      risk of death (sensitivity: 100%-100%, specificity: 57.1%-71.4%, area under the 
      curve [AUC] 0.759-0.841, respectively), whereas IL-1Ra concentrations below 7033 
      pg/mL determined a high probability of survival (sensitivity: 60%, specificity: 
      100%, AUC 0.724). In addition, IFN-gamma levels were significantly higher in 
      survivors than in controls during the initial 2 weeks of observation. 
      CONCLUSIONS: Our data show that serum cytokine disturbance patterns have 
      prognostic significance in patients with septic shock admitted to the ICU. The 
      pattern, defined by an early response to continuously elevated anti-inflammatory 
      cytokine serum levels, is associated with an enhanced risk of a fatal outcome for 
      patients.
FAU - de Pablo, Raul
AU  - de Pablo R
AD  - Intensive Care Unit, Hospital Universitario Principe de Asturias, Alcala de 
      Henares, Madrid, Spain. raul.depablo@uah.es
FAU - Monserrat, Jorge
AU  - Monserrat J
FAU - Reyes, Eduardo
AU  - Reyes E
FAU - Diaz-Martin, David
AU  - Diaz-Martin D
FAU - Rodriguez Zapata, Manuel
AU  - Rodriguez Zapata M
FAU - Carballo, Fernando
AU  - Carballo F
FAU - de la Hera, Antonio
AU  - de la Hera A
FAU - Prieto, Alfredo
AU  - Prieto A
FAU - Alvarez-Mon, Melchor
AU  - Alvarez-Mon M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Intensive Care Med
JT  - Journal of intensive care medicine
JID - 8610344
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Aged
MH  - *Critical Care
MH  - Female
MH  - Humans
MH  - Interferon-gamma/blood
MH  - Interleukin 1 Receptor Antagonist Protein/blood
MH  - Interleukin-1beta/blood
MH  - Interleukin-6/blood
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - ROC Curve
MH  - Receptors, Tumor Necrosis Factor, Type I/blood
MH  - Receptors, Tumor Necrosis Factor, Type II/blood
MH  - Sensitivity and Specificity
MH  - Shock, Septic/*blood/*mortality/pathology
MH  - Tumor Necrosis Factor-alpha/blood
EDAT- 2011/04/06 06:00
MHDA- 2011/08/13 06:00
CRDT- 2011/04/06 06:00
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2011/08/13 06:00 [medline]
AID - 0885066610384465 [pii]
AID - 10.1177/0885066610384465 [doi]
PST - ppublish
SO  - J Intensive Care Med. 2011 Mar-Apr;26(2):125-32. doi: 10.1177/0885066610384465.