Natural inhibitors of neutrophil function in acute respiratory distress syndrome

摘要

ObjectiveNeutrophils play a key role in the physiopathogenesis of acute lung injury in general and acute respiratory distress syndrome (ARDS) in particular. To identify the anti-inflammatory mediators with a protective effect on lung tissue damage in ARDS, we correlated the concentration of the Clara cell 16-kD protein (CC16; an inhibitor of neutrophil chemotaxis), angiogenin (an inhibitor of degranulation), and the total radical oxygen neutralizing activity with the amount of elastase (a marker of neutrophil activation) and with the Pao2/Fio2ratio, which is inversely related to lung injury.SettingUniversity hospital.PatientsPatients with ARDS (n equals; 12) and patients at risk for developing ARDS (n equals; 14).InterventionsPatients underwent bronchoalveolar lavage 12 hrs after diagnosis of ARDS or at-risk status.Measurements and Main ResultsThe amount of CC16 and radical oxygen neutralizing activity was not significantly different in patients with or at risk for ARDS. In contrast, the amount (mean plusmn; sem) of angiogenin in the bronchoalveolar lavage of ARDS patients (45 plusmn; 14 ng/mL, n equals; 12) was increased 11-fold (p .05) compared with patients at risk for ARDS (4 plusmn; 1 ng/mL, n equals; 14). In patients with ARDS, the amount of protein and angiogenin in bronchoalveolar lavage increased with decreasing concentration of CC16 (p .05). In addition, CC16 correlated with the Pao2/Fio2ratio (p .05) and inversely with the amount of elastase (p .05) and thus may be regarded as a reliable protective agent for lung injury.ConclusionA 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 influence the disruption of the balance between natural inflammatory and anti-inflammatory or protective factors, could be useful to modulate the tissue destruction and the course of ARDS.