Compartmentalisation of Cytokines and Cytokine Inhibitors in Ventilator-associated Pneumonia

Objective: To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP).

Design: Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA.

Setting: An adult medical and surgical university hospital intensive care unit.

Patients: Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls.

Interventions: None.

Results: Plasma concentrations of the measured cytokines and cytokine inhibitors did not change significantly in any patients. In control patients, NBL fluid concentrations of sIL-1RII decreased significantly over time (P=0.01). In patients who developed VAP, NBL fluid concentrations of TNFalpha, sTNFalphaRI, IL-1alpha, and IL-1beta increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/plasma concentration ratios for TNFalpha, sTNFalphaRI, IL-1alpha, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001, P=0.001, P=0.04, P=0.03, and P=0.04, respectively).

Conclusion: Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.