In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

Abstract

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. Aim: 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 alveolarcapillary 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. Conclusion: 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.

Oral Glutamine Attenuates Cyclophosphamide-Induced Oxidative Stress in the Bladder but Does Not Prevent Hemorrhagic Cystitis in Rats

“…Pretreatment with glutamine significantly attenuated CPinduced oxidative stress and neutrophil infiltration as evidenced by decrease in MPO activity, which is one of the markers of neutrophil infiltration [24]. However, surprisingly, glutamine did not prevent CP-induced bladder damage.…”

Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA-21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury

“…11 We previously reported that an intravenous β-agonist (salbutamol) reduced extravascular lung water in ARDS patients. [13][14][15][16] However, we found salbutamol significantly increased the 28-day mortality rate because of its side effects, such as tachycardia, arrhythmia, and lactic acidosis, in a multicenter, randomized, controlled clinical trial. 17 Therefore, new therapeutic agents need to be identified.…”

Keratinocyte growth factor for the treatment of the acute respiratory distress syndrome (KARE): a randomised, double-blind, placebo-controlled phase 2 trial

“…3. increases surfactant protein production. 4. downregulates pro-inflammatory cytokines and enhances endothelial cell resistance to injury and alters MMP release (Gillis, Savla et al 1999).…”

“…The pathogenesis of ARDS involves pulmonary neutrophil-and macrophage-driven inflammation, [3][4][5] and injury to the alveolar epithelium and endothelium. 2 The resolution of pulmonary oedema and improved outcome in ARDS is associated with enhanced alveolar epithelial function, suggesting that a strategy to accelerate epithelial repair in ARDS may be beneficial.…”