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Early Alterations in Neutrophil Activation Are Associated with Outcome in Acute Lung Injury

Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Science Center, Denver, Colorado; Chest Department, Taipei Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Correspondence and requests for reprints should be addressed to Dr. Edward Abraham M.D., Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Mail Code C-272, 4200 East Ninth Avenue, Denver, CO 80262. E-mail: Edward.Abraham{at}UCHSC.edu

Persistent elevations of proinflammatory cytokines in the lungs are associated with increased mortality from acute lung injury (ALI), suggesting that the degree of pulmonary inflammation is an important determinant of clinical course in ALI. The transcriptional regulatory factor nuclear factor-B (NF-B) is involved in modulating the expression of many cytokines and other proinflammatory mediators implicated in the development and progression of ALI. Because neutrophils appear to play a major role in the development of ALI, we examined the relationships between clinical outcome and activation of NF-B in peripheral neutrophils from patients (n = 30) with sepsis-induced ALI. We found that nuclear translocation of NF-B in this setting was dependent on the activation of p38 and Akt kinases. Diminished activation of NF-B or Akt, but not p38, in the early postintubation period was associated with less time on the ventilator and improved survival in critically ill patients with ALI. These results suggest that early alterations in neutrophil activation patterns, particularly involving the ability to accumulate NF-B to the nucleus after relevant stimuli, contribute to subsequent clinical course in ALI.

Key Words: neutrophils • transcription factors • signal transduction • cellular activation • lung

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