Theophylline alters neutrophil function in preterm infants.
Theophylline (1,3-dimethylxanthine), which is often prescribed to premature infants to treat apnea, acts, in part, by altering the metabolism of cyclic AMP. This second messenger plays a role in signal transduction mediating neutrophil functions, including respiratory burst, chemotaxis, and motility. We hypothesize that theophylline causes reduced respiratory burst activity, chemotaxis, and random motility in neutrophils. In these studies, we aim at determining the effects of theophylline on neutrophil function in vitro in cells from preterm and full-term infants and adults as well as on neutrophils obtained from premature infants receiving theophylline treatment. Neutrophils were obtained from 20 preterm infants, 16 full-term infants, and 14 adults. Chemiluminescence, chemotaxis, and random motility were measured after exposure of these cells to theophylline in vitro (0- 84 micromol/l or 0-15 microg/ml). In addition, these neutrophil activities were correlated with serum theophylline levels in 13 preterm infants receiving theophylline treatment for 72 h. Neutrophils from premature infants, term infants, and adults all displayed reduced chemiluminescence, chemotaxis, and random motility at 84 micromol/l (15 microg/ml) of theophylline in vitro. The relative reductions were greatest in cells from premature infants (p < 0.01). A level-dependent reduction in these activities was also noted in neutrophils from preterm infants with serum theophylline levels >46 micromol/l (8.2 microg/ml; p < 0.001). In contrast, lower theophylline concentrations (about 28 micromol/l or 5 microg/ml), either in vitro or in vivo, caused significant increases in neutrophil activities. Theophylline concentrations in the high therapeutic range (84 micromol/l or 15 microg/ml) cause dose-dependent reductions in neutrophil chemiluminescence, chemotaxis, and random motility. Cells from preterm infants are particularly sensitive to this effect. In contrast, theophylline concentrations in the low therapeutic range (28 micromol/l or 5 microg/ml) cause increased neutrophil activities. Altered neutrophil activity in newborns related to theophylline treatment may affect the infants' response to infection as well as the incidence of inflammatory diseases.
Mehta
Rajeev
R
Department of Pediatrics/Neonatology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. mehtara@umdnj.edu
Weinberger
Barry
B
Usmani
Shaista S
SS
Wapnir
Raul A
RA
Harper
Rita G
RG
D001993:Bronchodilator Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology*
D001993:Bronchodilator Agents; D013806:Theophylline