Inhalation of lipopolysaccharide (LPS) by humans rapidly recruits neutrophils to alveolar structures. Recruitment of neutrophils may be mediated in pad by intrapulmonary release of cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-8, although the kinetics of cytokine accumulation and neutrophil recruitment to the lungs after LPS inhalation have not been determined. Release of some cytokines in response to LPS is reported to be decreased in smokers' alveolar macrophages compared with nonsmokers', suggesting responses to LPS may differ in smokers (S) and nonsmokers (NS). To assess the kinetics of early cytokine accumulation after LPS inhalation and to compare inflammation induced in LPS-exposed S and NS, we performed bronchoalveolar lavage (BAL) in 28 subjects (14 NS and 14 S) at 90 or 240 minutes after inhalation of aerosolized LPS (30 μg). BAL performed at 90 and 240 minutes after LPS inhalation recovered increased numbers of neutrophils and lymphocytes in both NS and S compared with an unexposed control group (10 NS, 10 S), with greater recovery of neutrophils in S than NS (p < 0.001). BAL fluid supernate concentrations of IL-8, IL-1β, and tumor necrosis factor-α at 90 minutes were increased in S and NS compared with an unexposed control group. IL-8 and tumor necrosis factor-α concentrations were similar in S and NS; however, IL-1β concentrations were greater in S (p < 0.005). BAL fluid concentrations of IL-1β and IL-8 at 90 minutes correlated with absolute neutrophil recovery in S and NS. These findings suggest that the rapid accumulation of cytokines, particularly IL-1β and IL-8, contributes to lung neutrophil recruitment after LPS inhalation. In addition, parameters of pulmonary inflammation present in S after LPS inhalation are similar to or increased compared with those present in NS.
ASJC Scopus subject areas
- Pathology and Forensic Medicine