Compartmentalized cytokine production during mechanical ventilation and ventilator-associated pneumonia

Ventilator associated pneumonia (VAP) is a common and serious complication of mechanical ventilation (MV). In pneumonia, host defense is considered to be dependent upon the expression of pro-inflammatory cytokines (e.g., tumor necrosis factor-α (TNF), and interleukin (IL)-6), anti-inflammatory cytokines (e.g., IL-10), and cytokines with chemotactic abilities (e.g., IL-8).

We hypothesized that during VAP the inflammatory response is restricted to the side of infection, i.e., to the lung, and may raise before the diagnosis of VAP is clinically made. Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require MV for longer than 5 days. Prior to the NBL, blood samples were drawn. The diagnosis of VAP was standardized using a Clinical Pulmonary Infection Score.

VAP occurred in nine patients and the 19 patients who did not develop VAP were considered controls. There were no differences between patients with VAP and controls with respect to age, gender, initial APACHE II score, and primary diagnosis. Levels of TNF, IL-10, IL-6 and IL-8 did not change in control patients in either plasma or NBL-fluid. Furthermore, the diagnosis of VAP was not associated with changes in plasma cytokines. However, serial changes in TNF, IL-10, IL-6 and IL-8 in NBL-fluid strongly correlated with the diagnosis of VAP. A rise of TNF in NBL-fluid above 200 pg/ml predicted a 4.0 (95% CI: 1.1–15.1) times increased risk for developing VAP (P = 0.04, time-dependent Cox proportional hazard analysis). An increase of IL-10, IL-6 and IL-8 levels in NBL-fluid above 100 pg/ml, 1 ng/ml, and 15 ng/ml, respectively, was associated with a relative risk of 5.6 (95% CI: 1.5–20.9), 9.0 (95% CI: 1.1–72.1), and 4.6 (95% CI: 0.9–22.6), respectively, for developing VAP.

Local, but not systemic, cytokine levels increase before VAP is clinically diagnosed.

Affiliations

1. Intensive Care Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK
   • J Millo
   •  & CS Garrard
2. Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, Meibergdreef 9, 1105 AZ, The Netherlands
   • MJ Schultz
3. Laboratory of Experimental Internal Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands
   • MJ Schultz
   •  & T van der Poll
4. Clinical Epidemiology and Biostatistics, Academic Medical Center, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands
   • GJ Weverling
5. Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Meibergdreef 9, Amsterdam, AZ, 1105, The Netherlands
   • T van der Poll

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