On the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury.

Management of acute respiratory distress syndrome (ARDS) lial permeability [13]), altered membrane lipid trafficking (14), and increased activity of stress-responsive genes (15) has improved in recent years, resulting in a decrease in mortality (1, 2), although precise reasons for this are still debated. that may participate in the genesis of VILI. Severe alterations (cell lysis, basement membrane denudation [3]) may favor Physiologic and clinical research has been directed at determining whether the lesions produced by injurious ventila-lung neutrophil adhesion and the activation and release of inflammatory mediators. The lungs are clearly greatly inflamed tion in laboratory animals, termed " ventilator-induced lung injury " (VILI) (3), have their counterpart in humans called at later stages of VILI, as evidenced by their infiltration by leukocytes (16, 17). The aim of this paper is to highlight several ventilator-associated lung injury (4). This work recently culminated in the demonstration of a 22% reduction in mortality inconsistencies in the experimental and clinical evidence of of patients with ARDS ventilated with a reduced Vt. The cytokine production during injurious ventilation that ques-reason why such a simple strategy reduces mortality is not tion the role of cytokines during VILI. obvious but, in any case, it is not related to gross barotrauma reduction (5). Investigators suggest that it might be due to EFFECTS OF STRETCHING CELLS ON THE RELEASE less lung and systemic inflammation, as attested by lower OF CYTOKINES AND CHEMOKINES plasma interleukin (IL)-6 concentrations in patients venti-Human alveolar macrophages subjected to prolonged (24 hours) lated with a low Vt (5). This is in keeping with clinical findings cyclic stretching (considered as an in vitro analog of high volume of lower bronchoalveolar lavage (BAL) fluid and serum cyto-mechanical ventilation) release IL-8, a chemokine involved in kine concentrations in patients ventilated with 7.6 ml/kg com-polymorphonuclear recruitment, but not cytokines such as tumor pared with 11.1 ml/kg Vt (6). Moreover, the possibility that necrosis factor (TNF)-␣ or IL-6 (18). Concordant findings were multiple-system organ failure frequently observed in patients reported with the human alveolar epithelial cell line (A459) (19). with ARDS could be caused by inappropriate ventilator set-The release of the chemoattractant IL-8 by isolated cells may tings has been explicitly raised (7–9). help explain the neutrophil infiltration that occurs later during It is also quite possible that changes in cytokine concentrations are unrelated to mechanical ventilation, which merely These studies suggest that stretching cells that are normally permits …