Theophylline inhibits the production of nitric oxide by peripheral blood mononuclear cells from patients with asthma

Background: Nitric oxide (NO), a reactive free radical synthesized from L-arginine by the enzyme NO synthase (NOS), may play a role in many pathophysiologic conditions, including asthma. Objective: The aim of this study was to investigate whether peripheral blood mononuclear cells (PBMCs) from asthmatics would spontaneously produce NO. A second objective was to ascertain whether commonly used asthma medications would modulate the production of NO. Methods: PBMCs were isolated from 24 subjects (10 with asthma, 4 with allergic rhinitis and 10 healthy controls) and were incubated either alone or in the presence of an RNA polymerase inhibitor (actinomycin D, 1 mu g/mL), a NOS inhibitor (L-N-G-nitroarginine methyl eater [L-NAME], 1 mM), and L-NAME plus L-arginine (5 mM). Furthermore, PBMCs were incubated with or without addition of thera therapeutic concentrations of hydrocortisone (15 mu g/mL), theophylline (15 mu g/mL), albuterol (15 mu g/mL) and ipratropium bromide (12 mu g/mL). Culture supernatants were collected and assayed for NO production. Results: NO production was significantly elevated in asthmatics compared with the control group (1.39 +/- 0.21 mu M versus 0.46 +/- 0.01 mu M; P <.05). L-NAME significantly reduced NO production in asthmatics (0.83 +/- 0.06 mu M; P <.05), an effect completely reversed by L-arginine. Theophylline blocked NO production in asthmatics (1.39 1 0.21 mu M to 0.92 +/- 0.11; P <.05). There was no significant effect with any of the other medications. Conclusion: This study suggests that theophylline may be antiinflammatory by inhibiting the L-arginine-dependent production of NO in patients with asthma.