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(Journal of Leukocyte Biology. 2000;68:194-200.)
© 2000 by Society for Leukocyte Biology

Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

Correspondence: Kozo Yasui, Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. E-mail: koyasui{at}gipac.shinshu-u.ac.jp

The understanding of theophylline as a bronchodilator has been reconsidered in recent years. We undertook to determine its immunomodulatory actions in granulocytes and elucidate their mechanism. Preincubation of neutrophils with theophylline (10^-5 to 5 x 10^-3 M) had a biphasic effect on O₂^- production stimulated with N-formyl-methionyl-leucyl-phenylalanine or C5a. Theophylline potentiates O₂^- production via adenosine A_2A receptor antagonism induced by receptor-linked agonists from neutrophils, but not from eosinophils. The addition of theophylline caused a significant decline in neutrophil chemotaxis at lower concentrations than those for eosinophil motility. Theophylline reduces neutrophil chemotaxis via adenosine A₁ receptor antagonism. At high concentrations, with an intracellular cAMP accumulation as a result of phosphodiesterase (PDE) inhibition, theophylline also exerts an inhibitory effect on the O₂^- production and chemotaxis of both types of cells. The difference in theophylline’s effect on neutrophils and eosinophils appears to depend on the existence of specific adenosine receptors. Theophylline thus modulates granulocyte functions in association with specific adenosine receptor antagonism and cAMP-PDE inhibition.

Key Words: superoxide anion production • chemotaxis • adenosine • receptor antagonism • airway inflammation

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