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. 2009;13(6):R172.
doi: 10.1186/cc8148. Epub 2009 Nov 2.

Decrease of CD4-lymphocytes and apoptosis of CD14-monocytes are characteristic alterations in sepsis caused by ventilator-associated pneumonia: results from an observational study

Aimilia Pelekanou  1 , Iraklis Tsangaris, Antigoni Kotsaki, Vassiliki Karagianni, Helen Giamarellou, Apostolos Armaganidis, Evangelos J Giamarellos-Bourboulis
Affiliations

Decrease of CD4-lymphocytes and apoptosis of CD14-monocytes are characteristic alterations in sepsis caused by ventilator-associated pneumonia: results from an observational study

Aimilia Pelekanou et al. Crit Care. 2009.

Abstract

Introduction: The present study aimed to investigate changes of the immune response between sepsis due to ventilator-associated pneumonia (VAP) and sepsis due to other types of infections.

Methods: Peripheral venous blood was sampled from 68 patients with sepsis within 24 hours of diagnosis; 36 suffered from VAP; 32 from other nosocomial infections, all well-matched for severity, age and sex. Blood monocytes were isolated and cultured with/without purified endotoxin (lipopolysaccharide (LPS)). Estimation of tumour necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) in cultures' supernatants was done by an enzyme immunoassay. Flow cytometry was used to determine subpopulations of mononuclear cells and apoptosis. To mimic pathogenesis of VAP, mononuclear cells of healthy volunteers were progressively stimulated with increased inocula of pathogens; apoptosis was determined.

Results: In patients with VAP, the absolute number of CD3(+)/CD4(+) lymphocytes was significantly lower (P = 0.034) and apoptosis of isolated monocytes was increased (P = 0.007) compared to other infections. TNFalpha and IL-6 production from LPS-stimulated monocytes was lower in patients with VAP-related sepsis than with sepsis due to other infections. Apoptosis of monocytes was induced after in vitro stimulation of mononuclear cells by a mechanism mimicking VAP.

Conclusions: Decrease of CD4-lymphocytes and immunoparalysis of monocytes are characteristic alterations of sepsis arising in the field of VAP.

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Figures

Figure 1
Figure 1
TNFα and IL-6 production from the supernatants of monocytes. Concentrations of TNFα and IL-6 of supernatants of monocytes of patients with sepsis due to ventilator-associated pneumonia (VAP) and patients with sepsis caused by other nosocomial infections. The asterisk denotes significant difference between the two groups of patients. (P = 0.008 for TNFα; P = 0.003 for IL-6). LPS = lipopolysaccharide; SE = standard error.
Figure 2
Figure 2
Comparison of survival of septic patients. Comparison of survival of septic patients due to ventilator-associated pneumonia (VAP) and patients with sepsis caused by other infections depending on the presence or absence of response of their monocytes to stimulation with lipopolysaccharide.
Figure 3
Figure 3
Apoptosis of CD14-monocytes and of CD4-lymphocytes of healthy volunteers. Induction of apoptosis of CD14-monocytes and inhibition of apoptosis of CD4-lymphocytes of healthy volunteers according to four different patterns of stimulation by isolates of Acinetobacter baumannii and of Pseudomonas aeruginosa. A = un-stimulated controls; B = three-step stimulation mimicking pathogenesis of ventilator-associated pneumonia (VAP); C = abrupt stimulation with pathogens of VAP; and D = abrupt stimulation mimicking pathogenesis of bacteremia. Asterisks denote significant difference between patterns B and D and between patterns B and A. SE = standard error.
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Comment in

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