INTERACTIONS BETWEEN NEUTROPHILS AND CYTOKINES IN BLOOD AND ALVEOLAR SPACES DURING ARDS

Although the pathogenesis of the acute respiratory distress syndrome ( ARDS) is complex and poorly understood, several observations point to an important role of interactions between polymorphonuclear neutrophil s (PMN) and cytokines in this process. We therefore studied certain pa rameters involved in PMN transendothelial migration (adhesion molecule expression and cytoskeletal organization) in patients with ARDS (n = 14) in comparison with other ventilated patients (n = 15). We found th at in the basal state, both whole-blood PMN and alveolar PMN obtained by bronchoalveolar lavage (BAL) were activated, as shown by decreased L-selectin CD62L and increased beta 2 integrin CD11b expression, as we ll as decreased F-actin content. The degree of PMN activation increase d with the degree of lung injury and with the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL -8). Moreover, the capacity of ex vivo stimulation of alveolar PMN by a bacterial peptide was low in ARDS and could partly account for the h igh susceptibility of these patients to lung infection. Therefore, ARD S-associated lung injury could be caused, at least in part, by inappro priate adhesion and transendothelial migration of proinflammatory cyto kine-primed PMN.