In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury.
BACKGROUND
Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS.


OBJECTIVE
To investigate the effects of salbutamol on neutrophil function.


METHODS
The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days' treatment with placebo or salbutamol (ALI/ARDS group). Alveolar-capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured.


RESULTS
In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar-capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils.


CONCLUSIONS
At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways.
Perkins
G D
GD
Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. gavin.perkins@virgin.net
Nathani
N
N
McAuley
D F
DF
Gao
F
F
Thickett
D R
DR
D000420:Albuterol / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018375:Neutrophil Activation / Q000502:physiology; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D000420:Albuterol