The effects of β2-agonists and methylxanthines on neutrophil function in vitro

The effects of β2-agonists and methylxanthines on neutrophil function in vitro. C.G. Llewellyn-Jones, R.A. Stockley. ERS Journals Ltd 1994. ABSTRACT: Therapeutic agents which affect polymorphonuclear neutrophil (PMN) functions have the potential to reduce or increase PMN activation and, hence, influence the progression of lung inflammation. We have assessed the effects of the β2-agonist, terbutaline, and the methylxanthine, aminophylline, on PMN functions in vitro at both therapeutic and higher concentrations. At therapeutic levels, both agents increased PMN chemotaxis to formyl-methionylleucyl-phenylalanine (FMLP) in a dose-dependent manner from a control value of 22.5±3.58 cells·field-1 to 26.1±4.73 cells·field-1 with 4 mg·l-1 terbutaline, and to 26.3±4.49 cells·field-1 with 20 mg·l-1 aminophylline. When the cells were preincubated with higher doses of the agents in separate experiments there was inhibition of chemotaxis from a control value of 31.1±2.06 cells·field-1 to 18.3±0.82 cells·field-1 at 160 mg·l-1 terbutaline, and to 16.1±0.77 cells·field-1 at 400 mg·l-1 aminophylline. A similar effect was seen when the PMNs were preincubated with terbutaline and aminophylline prior to assessment of superoxide anion generation, with stimulation of superoxide release at therapeutic levels of the drugs and inhibition at higher doses (19% increase from resting control cells at terbutaline 4 mg·l-1 and 53% reduction at 160 mg·l-1; 28% increase with aminophylline 20 mg·l-1 and 22% reduction at 400 mg·l-1). Both terbutaline and aminophylline had no effect on PMN degranulation, as assessed by the degradation of fibronectin. These data suggest that terbutaline and aminophylline exert a biphasic effect on PMN functions in vitro, and may have detrimental effects on lung tissues at therapeutic levels through potentiation of PMN recruitment and activation. However, the observed effects of therapeutic doses of these agents on in vitro PMN functions were relatively small and, therefore, the clinical relevance of these results is, as yet, uncertain. Eur Respir J., 1994, 7, 1460–1466. The Lung Immunobiochemical Research Laboratory, The General Hospital, Birmingham, UK.