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Comparative Study
. 2006;10(3):R76.
doi: 10.1186/cc4921. Epub 2006 May 12.

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

Evangelos J Giamarellos-Bourboulis  1 , Christina Routsi, Diamantis Plachouras, Vassiliki Markaki, Maria Raftogiannis, Dimitrios Zervakis, Vassilios Koussoulas, Stylianos Orfanos, Anastasia Kotanidou, Apostolos Armaganidis, Charis Roussos, Helen Giamarellou
Affiliations
Comparative Study

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

Evangelos J Giamarellos-Bourboulis et al. Crit Care. 2006.

Abstract

Introduction: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome.

Methods: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFalpha) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFalpha, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay.

Results: Mortality rates of patients with apoptosis < or =50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis < or =50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis < or =50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFalpha were higher in patients with monocyte apoptosis < or =50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5.

Conclusion: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis.

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Figures

Figure 1
Figure 1
Monocytes apoptosis of two septic patients after flow cytometric analysis; ANNEXIN-V(+)PI(-) cells (region H4) are considered apoptotic.
Figure 2
Figure 2
Apoptosis of monocytes of 36 patients with septic shock in relation to final outcome. Circles denote outliers and asterisks extremes.
Figure 3
Figure 3
Comparative survival of 36 patients with septic shock in relation to monocyte apoptosis of the first day (≤50% or >50%).
Figure 4
Figure 4
Ex vivo production of TNFα and IL-6 by first day monocytes in relation to apoptosis, without (-) / with (+) triggering by LPS. Circles denote outliers and asterisks extremes. a: response lower than controls
Figure 5
Figure 5
Comparative concentrations of IL-6 and IL-8 over follow-up of patients with septic shock in relation to monocyte apoptosis of the first day
Figure 6
Figure 6
ROC curves of ≥50% apoptosis of monocytes of the first day for survival and for diagnosis of septic shock.
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