Cg. Llewellynjones et Ra. Stockley, THE EFFECTS OF BETA(2)-AGONISTS AND METHYLXANTHINES ON NEUTROPHIL FUNCTION IN-VITRO, The European respiratory journal, 7(8), 1994, pp. 1460-1466
Therapeutic agents which affect polymorphonuclear neutrophil (PMN) fun
ctions have the potential to reduce or increase PMN activation and, he
nce, influence the progression of lung inflammation. We have assessed
the effects of the beta(2)-agonist, terbutaline, and the methylxanthin
e, aminophylline, on PMN functions in vitro at both therapeutic and hi
gher concentrations, At therapeutic levels, both agents increased PMN
chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP) in a dose-d
ependent 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 experime
nts 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) te
rbutaline, and to 16.1+/-0.77 cells.field(-1) at 400 mg.l(-1) aminophy
lline. 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 leve
ls of the drugs and inhibition at higher doses (19% increase from rest
ing control cells at terbutaline 4 mg.l(-1) and 53% reduction at 160 m
g.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. The
se data suggest that terbutaline and aminophylline exert a biphasic ef
fect on PMN functions in vitro, and may have detrimental effects on lu
ng tissues at therapeutic levels through potentiation of PMN recruitme
nt and activation. However, the observed effects of therapeutic doses
of these agents on in vitro PMN functions were relatively small and, t
herefore, the clinical relevance of these results is, as yet, uncertai
n.