Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia

Abstract

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) α, interleukin (IL)-1α, IL-1β, IL-6, and IL-10 and the cytokine inhibitors soluble TNFα receptor type I (sTNFαRI), 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 TNFα, sTNFαRI, IL-1α, and IL-1β increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/ plasma concentration ratios for TNFα, sTNFαRI, IL-1α, 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.