Natural inhibitors of neutrophil function in acute respiratory distress syndrome

Objective. Neutrophils play a key role in the physiopathogenesis of acute l ung injury in general and acute respiratory distress syndrome (ARDS) in par ticular. To identify the anti-inflammatory mediators with a protective effe ct on lung tissue damage in ARDS, we correlated the concentration of the Cl ara cell 16-kD protein (CC16; an inhibitor of neutrophil chemotaxis), angio genin (an inhibitor of degranulation), and the total radical oxygen neutral izing activity with the amount of elastase (a marker of neutrophil activati on) and with the Pa-O2/F-IO2 ratio, which is inversely related to lung inju ry. Setting. University hospital. Patients. Patients with ARDS (n = 12) and patients at risk for developing A RDS (n = 14). Interventions. Patients underwent bronchoalveolar lavage 12 hrs after diagn osis of ARDS or at-risk status. Measurements and Main Results. The amount of CC16 and radical oxygen neutra lizing activity was not significantly different in patients with or at risk for ARDS. In contrast, the amount (mean +/- sem) of angiogenin in the bron choalveolar lavage of ARDS patients (45 +/- 14 ng/mL, n = 12) was increased 11-fold (p < .05) compared with patients at risk for ARDS (4 +/- 1 ng/mL, n = 14). In patients with ARDS, the amount of protein and angiogenin in bro nchoalveolar lavage increased with decreasing concentration of CC16 (p < .0 5). In addition, CC16 correlated with the Pa-O2/F-IO2 ratio (p < .05) and i nversely with the amount of elastase (p < .05) and thus may be regarded as a reliable protective agent for lung injury. Conclusion. A high concentration of CC16, a natural inhibitor of neutrophil function, decreases neutrophil-mediated lung damage of patients with ARDS. Strategies to increase natural anti-inflammatory agents, and thus influenc e the disruption of the balance between natural inflammatory and anti-infla mmatory or protective factors, could be useful to modulate the tissue destr uction and the course of ARDS.